eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
vol. 73
Original paper

Comprehensive immunohistochemical analysis based on the origin of leiomyosarcoma

Deniz Bayçelebi
Mehmet Kefeli
Levent Yıldız
Filiz Karagöz

Department of Pathology, Faculty of Medicine, Ondokuz Mayls University Samsun, Atakum/Samsun, Turkey
Pol J Pathol 2022; 73 (3): 233-243
Online publish date: 2023/01/10
Article file
- Comprehensive.pdf  [0.54 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
PlumX metrics:


Leiomyosarcoma (LMS) is the most common sarcoma of the uterus, representing 40–50% of all sarcomas and 1–3% of all uterine malignancies [1–4]. It can occur in any part of the body, especially in the uterus, retroperitoneum, extremities, abdomen, and visceral regions [5]. It is stated to originate from smooth muscle cells or precursor mesenchymal stem cells, which differentiate into smooth muscle cells [6].
Diagnostic criteria, molecular features, prognosis, treatments, and sensitivity to treatment differ depending on uterine and extra-uterine locations of LMS [6–12]. For example, a smooth muscle tumor in soft tissue can be considered malignant due to cytological atypia or high mitotic activity, while the same finding can be interpreted as bizarre leiomyoma or mitotically active leiomyoma, which are benign leiomyoma variants of the uterus [11, 13–17]. Immuno-profile of tumors may be important for patients’ treatment options. Some authors suggested aromatase inhibitors for the treatment of hormone receptor-positive LMS [18]. In addition, retroperitoneum and deep soft tissue tumors can reach large sizes and metastasize without symptoms, while those with subcutaneous localization are diagnosed early and almost never metastasize.
Leiomyosarcoma pathogenesis involves several functional gene families related to cell cycle regulation, cell homeostasis, signal transduction, growth factors, transcription factors, and oncogenes [3, 19–24]. Molecular sub-typing to determine the origin of these tumors has not yet been clarified, and the distinction in problem cases is largely based on clinical consensus [3]. Therefore, new auxiliary methods are needed to determine the origin of these tumors, which are genetically heterogeneous and complex. In this study, we aimed to investigate whether there is a difference in staining between LMS originating from the uterus and extra-uterine, and the value of detected data in the differentiation of these tumor groups by using a large immunohistochemical panel. The selection of immune markers primarily aimed to determine the origin of tumor. The panel was expanded with other antibodies, which were identified in previous studies and thought to may be significant in terms of tumor progression, differentiation, survival, and treatment efficacy. We also compared the immunohistochemical characteristics of uterine LMS with those of abdominal/ retroperitoneal origin, which are problematic in clinical recognition, and also have different diagnostic criteria and treatment protocols.

Material and methods

Case selection
Twenty males and 22 females with extra-uterine LMS (EU-LMS), and 29 uterine LMS (U-LMS) cases diagnosed with primary LMS between 2006 and 2018 at our pathology department were included in this study. Histopathological features of smooth muscle tumors, including cellularity, mitotic rate, cytological atypia, and tumor cell necrosis were analyzed and recorded. According to the current World Health Organization (WHO) diagnostic criteria, uterine LMS is diagnosed as spindle cell smooth muscle tumor when the tumor has at least two of the following criteria: marked cytological atypia (2+/3+), tumor cell necrosis, and high mitotic rate (≥ 4 mitoses/mm2) [25]. Myxoid and epithelioid types of tumor were not included in the study. For extra-uterine LMS, the current WHO diagnostic criteria were used based on their localizations [26–28]. In all cases, sections stained with hematoxylin and eosin were re-examined, and the best samples were selected for tissue micro-array. Current medical records and clinical information of cases were scanned from computer records and reviewed. The study was granted approval by the relevant institutional ethics committee (approval number: OMU KAEK 2018/159).
Tissue micro-arrays and immunohistochemistry
Necrosis-free areas and parts that represented the tumor best in the hematoxylin and eosin stained slides were identified and removed from the block. Two samples for each case were embedded in 3 paraffin blocks with 60 cavities, each with a diameter of 1 mm. Immunohistochemical tests were applied to each block with 20 antibodies. Nuclear with estrogen receptor (ER), progesterone receptor (PR), FOXM1, CDK4, MDM2, c-Myc, PAX8, c-erb-B2, cyclin D1, p53, cytoplasmic and nuclear with WT-1, p16, bcl-2, membranous with EMMPRIN, and cytoplasmic staining with c-kit, fascin, calponin, SMA, desmin, and caldesmon were evaluated (Table 1). P-value < 5% staining was accepted as negative, and 6–100% staining was accepted as positive.
Statistical method
One-sample Kolmogorov-Smirnov and t-test were used to evaluate age distribution in statistical evaluation. Categorical data were compared with 2 test. The staining features of 20 immunohistochemical markers were compared in 2 groups with U-LMS and EU-LMS cases, and in 3 groups with U-LMS, females and males EU-LMS cases. P-value < 0.05 was considered significant.


Demographic information
Of the 71 cases included in the study, 29 (41%) were U-LMS, and 42 (59%) were EU-LMS cases. Twenty- two (52%) of EU-LMS cases were females, and 20 (48%) were males. Fourteen of EU-LMS tumors were located in the extremities, 8 in the retroperitoneum, 6 in the abdomen, 6 in the skin, 4 in the intestine, 3 in the head and neck region, 3 in the testis, and 1 in the thorax. The mean age of all cases was 57.0 ±15.2 years (range, 18–79 years). The mean age of U-LMS cases was 52.5 ±9.8 years (range, 28–76 years), the mean age of EU-LMS cases was 60.0 ±17.5 years (range, 18–79 years), and the difference between the two groups was statistically significant, with p = 0.026. In EU-LMS cases, the age difference between female (59.0 ±15.8 years) and male (61.0 ±19.6 years) genders was not significant (p > 0.05) (Table 2).
Immunohistochemical findings
U-LMS cases were stained with ER, PR, desmin, and EMMPRIN at a higher rate than EU-LMS cases (p < 0.05) (Fig. 1). When EU-LMS cases were considered as two different groups according to female and male genders and three groups were evaluated separately, the U-LMS cases were stained more with ER, PR, desmin (p < 0.05) compared with EU-LMS cases. While the male and female EU-LMS cases were compared, no significant staining difference was found (p > 0.05). When EMMPRIN positivity was evaluated between the three groups, the difference in staining was not statistically significant (p > 0.05) (Table 3).
EU-LMS cases were stained with caldesmon, c-Myc, and cyclin D1 at a higher rate than U-LMS cases (p < 0.05) (Fig. 2). When EU-LMS cases were considered as two different groups according to female and male genders, the only difference in the c-Myc staining among these three antibodies was found statistically significant among the three groups (p < 0.05) (Table 3).
There was not any statistically significant differences between cases U-LMS and EU-LMS regarding WT-1, SMA, calponin, CDK4, bcl-2, p53, p16, FOXM1, fascin, and CD117 staining (p > 0.05) (Table 4). No staining was detected in any of the cases in the immunohistochemical evaluation with C-erb-b2, PAX8, and MDM2.
Staining of LMS located in the retroperitoneum (n = 8) and abdomen (n = 6), which are clinically more problematic due to their site in terms of differential diagnosis with U-LMS and staining differences with U-LMS, are summarized in Table 5. There was no statistically significant differences between the groups (p > 0.05).


Many immunohistochemical markers have been previously investigated to determine the histopathological diagnosis, origin, and behavior of LMS [13–16, 22, 29–38]. In the selection of immunomarkers, the primary aim was to determine the origin of the tumor. In addition, it was aimed to establish the staining status and the presence of differences in U-LMS and EU-LMS of the markers discussed in various studies in terms of tumor progression, survival indicator, and treatment efficacy. Steroid hormone receptors (ER, PR), mullerian transcription markers (WT1, PAX8), smooth muscle markers (SMA, desmin, caldesmon, and calponin), markers that may contribute to treatment efficacy (CD117), and markers effective in tumor progression (EMMPRIN, fascin, c-Myc, MDM2, FOXM1, cyclin D1, CDK4, bcl-2, p16, p53, and c-erb-B2) were selected for the current study.
Steroid hormone receptors are one of the most commonly used markers in routine practice to differentiate U-LMS and EU-LMS. Statistically significant results were obtained in previous studies evaluating ER and PR positivity rates in U-LMS and EU-LMS. Rao et al. reported ER positivity in 12.5% of EU-LMS cases (2 of 16 tumors) and 71% of U-LMS cases (10 of 14 tumors). It was reported that a stained case in the EU-LMS group was localized in the retroperitoneum, and stained focal and weakly positive. The other case was located in the upper extremity, and stained focal and edge only [39]. Kelley et al. reported ER positivity in 87% of cases (13 of 15 tumors), and PR positivity in 80% (2 of 16 tumors) of U-LMS. Whereas ER positivity in 25% (4 of 16 tumors, 3 of which were female cases), and PR in 13% (2 of 16 tu-­ mors) of EU-LMS were detected. They observed that all EU-LMS cases showed only weak (1+: 1 to 25% of nuclei stained) ER and PR immunoreactivity, except for one case, which was stained intensely (4+: 76–100% of nuclei stained). The relatively higher staining rate of EU-LMS cases compared with other studies can be explained by taking the cut-off value as 1% in this study. Intense (4+) ER and PR staining was detected in a 61-year-old female patient, with a solitary tumor in the lower thoracic vertebral region and no primary U-LMS. Although the authors thought that this case may be an undiagnosed U-LMS due to previous hysterectomy for uterine fibroid, it was reported that hematoxylin-eosin-stained sections taken from the hysterectomy sample were leiomyoma only, and did not show any recurrence [40]. In Carvalho et al. study, ER positivity in 63% (19 of 30 tumors) and PR positivity in 73% (22 of 30 tumors) of U-LMS cases were reported. While 23% (11 of 48 tumors) of EU-LMS cases were ER-positive, PR positivity was reported in 40% cases (19 of 48 tumors), with a higher rate compared with the literature. It was stated that significant ratio of positively stained cases were weakly positive [41]. Lee et al. reported ER positivity in 50% (51 of 102 tumors) of U-LMS and 3% (4 of 140 tumors) of EU-LMS cases. In that study [9], the locations of ER-positive EU-LMS included one in male’s genital region, one in male’s rectal region, and two in female’s abdominal/pelvic region. In the current study, 48% (14 of 29 tumors) of U-LMS cases and 12% (5 of 42 tumors) of EU-LMS cases were stained positively with ER, similar to previous studies. Two of the ER-positive EU-LMS cases were females, and three were males. Two of these tumors were of abdominal origin. 62% of U-LMS (18 of 29 tumors) and 21% of EU-LMS (9 of 42 tumors) cases were positive for PR in our cohort. In a study by Carvalho et al., ER or PR positivity in EU-LMS cases was more common in female cases (15 of 24 female cases (63%) vs. 6 of 24 male cases (25%)) [41]. In the present study, there was no significant difference in ER and PR staining when male and female cases of EU-LMS groups were compared (p > 0.05). The ER staining percentage of extra-uterine tumors was always above 70% in males, and the staining intensity varied as weak, moderate, and high. In females, LMS in the pelvic region was stained at high intensity and high rate, while the weak intensity and low rate ER staining in the calf was stained. It was observed that the case of LMS located in the chest wall in a male patient was stained with diffuse strong PR, and in a female patient, LMS located in the retroperitoneum was stained in weak intensity and low intensity. These findings suggested that hormone receptor positivity in LMS is a feature related to the tumor itself rather than gender.
WT-1, the transcription factor that plays a role in the development of the genitourinary system, has recently been defined as a guide in Müllerian differentiation. For this reason, its’ usability in differentiation of U-LMS and EU-LMS has been investigated by various authors. Lee et al. reported nuclear WT-1 staining of 8% (8 of 98 tumors) for U-LMS, whereas none for EU-LMS. The authors observed cytoplasmic WT-1 immunostaining in 55% (54 of 98 tumors) of U-LMS and 52% (68 of 131 tumors) of EU-LMS cases [9]. In Carvalho et al. study evaluating 30 cases of U-LMS and 48 cases of EU-LMS, nuclear WT-1 staining was detected in 11% of all tumors. 23% of U-LMS (7 of 30 tumors) and 6% of EU-LMS (3 of 48 tumors) were stained nuclear positive for WT-1. In this study, WT-1 positivity was found only in female cases and in ER-positive retroperitoneum and uterine tumors. Therefore, nuclear WT-1 expression was thought to identify a common subset of tumors that were likely Müllerian in a particular group of tumors in female cases [41]. Bing et al. also reported cytoplasmic WT-1 staining in 64% (16 of 25 tumors) of U-LMS in their cohort [42]. In the current study, 14% of U-LMS cases (4 of 29 tumors) and 5% of EU-LMS cases (2 of 42 tumors) were nuclear-positive for WT-1. One of the cases with positive nuclear staining in the EU-LMS group was in the retroperitoneum and the other was in the para-testicular location. Although nuclear WT-1 positivity was observed more frequently in U-LMS, this difference was not statistically significant (p < 0.05). In our study, all of the cases that demonstrated nuclear staining showed cytoplasmic staining as well. When nuclear and cytoplasmic staining are evaluated together, 34% (10 of 29 tumors) of U-LMS and 36% (15 of 42 tumors) of EU-LMS cases were stained for WT-1. There was no statistically significant staining between these two groups, both nuclear and cytoplasmic WT-1-positive.
EMMPRIN, also known as CD147, is a 58 kDa weight transmembrane protein that is encoded by BSG gene [17]. EMMPRIN activates the induction of matrix metalloproteinases, which are important for extra-cellular matrix degradation and tumor progression. Although its’ use in the differentiation of uterine smooth muscle tumors has been investigated, its’ place in differential diagnosis of U-LMS and EU-LMS has not been investigated before [31]. Although the difference in EMMPRIN staining between U-LMS and EU-LMS was significant in our study (69% vs. 45% positive, respectively; p = 0.04825), the difference in staining in U-LMS and female EU-LMS was insignificant, suggesting that EMMPRIN cannot be a reliable marker when distinguishing U-LMS and EU-LMS cases in routine practice.
In previous studies, staining frequencies of LMS with SMA, caldesmon, desmin, and calponin were investigated [43–45]. In Carvalho’s study, it was stated that EU-LMS were stained with SMA at a higher rate than U-LMS (100% vs. 87%, respectively). Higher rates of desmin staining were detected in uterine tumors (83%) and retroperitoneal tumors in female cases (86%), and caldesmon was stained at higher rates in retroperitoneal tumors, in all females (94%, 15 of 16 tumors). With calponin, a positivity of 87% (26 of 30 tumors) was detected in U-LMS and 92% (44 of 48 tumors) in EU-LMS [41]. In our study, the percentage of staining with SMA, desmin, caldesmon, and calponin was 96%, 79%, 69%, and 65% for U-LMS, and 88%, 50%, 88%, and 43% for EU-LMS, respectively (Tables 3, 4). It was thought that the statistically significant staining difference between these two groups resulted from the high desmin staining rate of U-LMS, similar to Carvalho’s research. In our study, when compared with Carvalho’s study, it was noted that staining with caldesmon in EU-LMS cases did not make any difference in female gender, but it was stained at a higher rate in EU-LMS. Demicco et al. in their studies on 203 EU-LMS and 181 U-LMS cases, indicated that loss of expression in muscle markers could be observed in LMS, associated with loss of differentiation [46]. In our study, it was thought that the reason for no staining with muscle markers in some LMS cases were poorly differentiated tumor areas or limited sampling with the tissue micro-arrays.
The expression of c-Myc in LMS cases has been investigated in several studies. Jeffers et al. reported c-Myc over-expression in 11 of 23 U-LMS cases, but this did not correlate with survival [47]. Tsiatis et al. detected nuclear c-Myc expression in 15 of 28 soft tissue LMS cases, and they reported that cases with c-Myc-positive tumors had significantly shorter metastasis-free survival intervals than cases with c-Myc-negative tumors [48]. Its’ place in the differentiation of U-LMS and EU-LMS has not been investigated before. In the present study, nuclear c-Myc expression was found at a higher rate in EU-LMS cases (10% vs. 33%), and this difference was statistically significant (p = 0.02).
Cyclin D1 and CDK4 amplification have been reported to be observed in various tumors, including sarcomas [49–52]. Rb-cyclin D1 pathway is thought to be a specific target for molecular abnormalities in soft tissue LMS, and cyclin D1 over-staining may indicate an alternative mechanism to bypass Rb-mediated inhibition of cell proliferation [53]. Lee et al. showed that cyclin D1 is known to be a sensitive and specific diagnostic immunomarker for the histologically higher-grade and clinically more aggressive endometrial stromal sarcoma (ESS) sub-type YWHAE-FAM22 ESS [54]. In our study, a higher rate of cyclin D1 staining was observed in EU-LMS cases compared with U-LMS (52% vs. 28%, respectively; p = 0.037). In the current study, as with other antibodies, cyclin D1-positive was evaluated as > 5%. As in a study of Lee et al., when ≥ 70% moderate to strong nuclear positivity was taken as a cut-off, positivity was observed in 2 U-LMS and 6 EU-LMS in our series. There was no significant difference between the two groups in regard to CDK4 [54].
Bcl-2 expression, which was previously investigated as an indicator of tumor behavior, prognosis, and survival for LMS showed a similar staining percentage in U-LMS and EU-LMS cases in the present study (p > 0.05) [29, 30, 38]. p53 gene mutation observed mostly in advanced stage and high-risk soft tissue sarcomas has been also investigated in U-LMS and EU-LMS in the literature, and was found to be stained relatively more frequently in U-LMS cases [54–60]. In a study of Lee et al., p53 was stained positively in 29% (25 of 87 tumors) of U-LMS cases and 22% (21 of 96 tumors) of EU-LMS cases [9]. It was thought that MDM2 could act independently and through p53 gene mutation, while MDM2 expression was found in U-LMS cases in several studies [39]. Hall et al. reported MDM2 over-expression of 13% (3 of 23 tumors), while Blom et al. reported 8% (4 of 49 tumors) in U-LMS cases [56–58]. In a study by Rao et al., it was stated that MDM2 amplification was more frequently seen in EU-LMS cases [39]. In our study, the staining difference in bcl-2, p53, and MDM2 was not significant in distinguishing U-LMS and EU-LMS cases (p > 0.05). This suggests that even though they are involved in oncogenesis, it will not contribute to differentiating them from other soft tissue sarcomas as well as determining the origin of U-LMS and EU-LMS.
Although most of the tumors outside the uterus are thought to be of vascular smooth muscle origin, Posligua et al. in their study conducted on 19 low-grade and 31 high-grade LMS cases shown that smooth muscle tumors observed in the peritoneum and retroperitoneum may be a second primary associated with secondary mullerian system rather than recurrence in follow-up of low-grade tumors. Staining differences supporting the possibility of independent tumors between U-LMS and EU-LMS were detected in 7 out of 10 cases with immunohistochemical markers (ER, WT1) [61]. When we compared U-LMS cases with retroperitoneal and abdominal LMS cases, we observed that ER, PR, and WT-1 were stained at a relatively lower rate in retroperitoneal LMS, while ER and WT-1 were stained in similar rates in abdominal LMS compared with U-LMS. Unlike Posligua’s study, we did not classify tumors as low- and high-grade in our study. However, as proposed by Posligua et al., it should be kept in mind that the possibility of retroperitoneal and peritoneal low-grade LMS may arise from a secondary Müllerian system, and they may have similar immuno-profile as uterine tumors.


In the current study conducted on 71 LMS cases using the tissue micro-array method, it was concluded that staining with ER, PR, desmin, and EMMPRIN might support the uterine origin, while caldesmon, c-Myc, and cyclin D1 may support the extra-uterine origin. The representation of a small part of the tumor due to the use of the tissue micro-array method in our study may have affected the staining results, especially for tumors with heterogeneous differentiation areas. Nevertheless, we think our study results should be considered in cost-effective planning while making differential diagnoses of U-LMS and EU-LMS using immunohistochemical method.


The authors would like to thank Dr Cihad Dündar for his supports in statistical analysis. The authors declare no conflict of interest.


1. Chiang S, Oliva E. Recent developments in uterine mesenchymal neoplasms. Histopathology 2013; 62: 124-137.
2. Crum CP, Nucci M, Howitt B, et al. Malignant leiomyosarcoma. In: Diagnostic gynecologic and obstetric pathology. Philadelphia, PA: Saunders/Elsevier 2017, 1737-58.
3. Guo X, Jo VY, Mills AM, et al. Clinically relevant molecular subtypes in leiomyosarcoma. Clin Cancer Res 2015; 21: 3501-3511.
4. Toledo G, Oliva E. Smooth muscle tumors of the uterus: a practical approach. Arch Pathol Lab Med 2008; 132: 595-605.
5. Lamm W, Natter C, Sophie S, et al. Distinctive outcome in patients with non-uterine and uterine leiomyosarcoma. BMC Cancer 2014; 14: 981.
6. Mangla A, Yadav U. Cancer. Leiomyosarcoma. Tresure Island, FL: StatPearls 2020
7. Billings SD, Folpe AL, Weiss SW. Do leiomyomas of deep soft tissue exist? An analysis of highly differentiated smooth muscle tumors of deep soft tissue supporting two distinct subtypes. Am J Surg Pathol 2001; 25: 1134-1142.
8. Horiuchi K, Yabe H, Mukai M, et al. Multiple smooth muscle tumors arising in deep soft tissue of lower limbs with uterine leiomyomas. Am J Surg Pathol 1998; 22: 897-901.
9. Lee CH, Turbin da, Sung VYC, et al. A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors. Mod Pathol 2009; 22: 1519-1531.
10. Paal E, Miettinen M. Retroperitoneal leiomyomas: a clinicopathologic and immunohistochemical study of 56 cases with a comparison to retroperitoneal leiomyosarcomas. Am J Surg Pathol 2001; 25: 1355-1363.
11. Weiss SW. Smooth muscle tumors of soft tissue. Adv Anat Pathol 2002; 9: 351-359.
12. Worhunsky DJ, Gupta M, Gholami S, et al. Leiomyosarcoma: one disease or distinct biologic entities based on site of origin? J Surg Oncol 2015; 111: 808-812.
13. Bodner-Adler B, Bodner K, Czerwnka K, et al. Expression of p16 protein in patients with uterine smooth muscle tumors: an immunohistochemical analysis. Gynecol Oncol 2005; 96: 62-66.
14. Miettinen M, Fetsch JF. Evaluation of biological potential of smooth muscle tumours. Histopathology 2006; 48: 97-105.
15. Mittal K, Demopoulos RI. MIB-1 (Ki-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Hum Pathol 2001; 32: 984-987.
16. O’Neill CJ, McBride HA, Connolly LE, et al. Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential. Histopathology 2007; 50: 851-858.
17. Xiong L, Edwards CK, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci 2014; 15: 17411-1741.
18. Thanopoulou E, Thway K, Khabra K, Judson I. Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors. Clin Sarcoma Res 2014; 4: 5.
19. Cui RR, Wright JD, Hou JY. Uterine leiomyosarcoma: a review of recent advances in molecular biology, clinical management and outcome. BJO 2017; 124: 1028-1037.
20. Dei Tos AP, Maestro R, Doglioni C, et al. Tumor suppressor genes and related molecules in leiomyosarcoma. Am J Pathol 1996; 148: 1037-1045.
21. Kawaguchi K, Oda Y, Saito T, et al. Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis. J Pathol 2003; 201: 487-495.
22. Kefeli M, Ylldlz L, Kaya FC, et al. Fascin expression in uterine smooth muscle tumors. Int J Gynecol Pathol 2009; 28: 328-333.
23. Makinen N, Vahteristo P, Kampjarvi K, et al. MED12 exon 2 mutations in histopathological uterine leiomyoma variants. Eur J Hum Genet, 2013; 21: 1300-1303.
24. Markowski DN, Huhle S, Nimzyk R, et al. MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors. Genes Chromosomes Cancer 2013; 52: 297-304.
25. Longacre TA, Lim D, Parra-Herran C. Uterine Leiomyosarcoma. In: World Health Organization Classification of Tumors of Female Genital Tumors. Lyon, France: IARC Press 2020, 283-285.
26. Dry SM, Fröhling S. Leiomyosarcoma. In: World Health Organization Classification of Tumors of Soft Tissue and Bone. Lyone, France: IARC Press 2020, 195-197 .
27. Billings SD, Panagopoulos I, Leiomyoma. In: World Health Organization Classification of Tumors of Soft Tissue and Bone. Lyon, France: IARC Press 2020, 188-189.
28. Folpe A, Eiston D, Kutzner H. Cutaneous leiomyosarcoma. In: World Health Organization Classification of Tumors of Skin Tumours. Lyone, France: IARC Press 2020, 330.
29. Bodner K, Bodner-Adler B, Kimberger O, et al. Bcl-2 receptor expression in patients with uterine smooth muscle tumors: an immunohistochemical analysis comparing leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma. J Soc Gynecol Investig 2004; 11: 187-191.
30. De Graaff MA, de Rooij MAJ, van den Akker BEWM, et al. Inhibition of Bcl-2 family members sensitises soft tissue leiomyosarcomas to chemotherapy. Br J Cancer 2016; 114: 1219-1226.
31. Kefeli M, Yildiz L, Gun S, et al. EMMPRIN (CD147) expression in smooth muscle tumors of the uterus. Int J Gynecol Pathol 2016; 35: 1-7.
32. Maekawa A, Kohanshi K, Setsu N, et al. Expression of Forkhead box M1 in soft tissue leiomyosarcoma: clinicopathologic and in vitro study using a newly established cell line. Cancer Sci 2016; 107: 95-102.
33. Oliva E, Young RH, Amin MB, et al. An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol 2002; 26: 403-412.
34. Özçelik B, Akgün H, SERiN IS et al. Uterin leiomyosarkomlarda C-kit pozitifliği ile Bcl-2 artlŞl araslndaki iliŞki. Türk Jinekolojik Onkoloji Dergisi 2004; 7: 59-65.
35. Raspollini MR, Amunni G, Villanucci A, et al. c-Kit expression in patients with uterine leiomyosarcomas: a potential alternative therapeutic treatment. Clin Cancer Res 2004; 10: 3500-3503.
36. Wang L, Felix JC, Lee JL, et al. The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus. Gynecol Oncol 2003; 90: 402-406.
37. Yildiz L, Kefeli M, Aydln, O et al. Fascin expression in melanocytic lesions of the skin. Eur J Dermatol 2009; 19: 445-450.
38. Zhai YL, Nikaido T, Toki T, et al. Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus. Br J Cancer 1999; 80: 1658-1664.
39. Rao UN, Finkelstein SD, Jones MW. Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas. Modern Pathology 1999; 12: 1001-1009.
40. Kelley TW, Borden EC, Goldblum JR. Estrogen and progesterone receptor expression in uterine and extrauterine leiomyosarcomas: an immunohistochemical study. Appl Immunohistochem Mol Morphol 2004; 12: 338-341.
41. Carvalho JC, Thomas DG, Lucas DR. Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups. Cancer 2009; 115: 4186-4195.
42. Bing Z, Pasha TL, Acs G, et al. Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors. Appl Immunohistochem Mol Morphol 2008; 16: 316-321.
43. Abeler VM, Nenodovic M. Diagnostic immunohistochemistry in uterine sarcomas: a study of 397 cases. Int J Gynecol Pathol 2011; 30: 236-243.
44. Hisaoka M, Wei-Qui S, Morio, T et al. Specific but variable expression of h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker. Appl Immunohistochem Mol Morphol 2001; 9: 302-308.
45. Rangdaeng S, Truong LD. Comparative immunohistochemical staining for desmin and muscle-specific actin. A study of 576 cases. Am J Clin Pathol 1991; 96: 32-45.
46. Demicco EG, Boland GM, Brewer Savannah KJ et al. Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value. Histopathology 2015; 66: 627-638.
47. Jeffers MD, Richmond JA, Macaulay EM. Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas. Mod Pathol 1995; 8: 701-704.
48. Tsiatis AC, Herceg ME, Keedy VL, et al. Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma. Mod Pathol 2009; 22: 1432-1438.
49. Hong A, Davies S, Steven G, et al. Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma. Appl Immunohistochem Mol Morphol 2004; 12: 26-30.
50. Horvai AE, Kramer MJ, O’Donnell R. Beta-catenin nuclear expression correlates with cyclin D1 expression in primary and metastatic synovial sarcoma: a tissue microarray study. Arch Pathol Lab Med 2006; 130: 792-798.
51. Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol 2009; 220: 292-296.
52. Lin L, Hicks D, Xu B, et al. Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma. Mod Pathol 2005; 18: 705-709.
53. Maelandsmo GM, Berner JM, Florenes VA, et al. Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas – relationship to amplification and mRNA levels of CDK4 and CCND1. Br J Cancer 1995; 72: 393-398.
54. Lee CH, Ali RH, Rouzbahman M, et al. Cyclin D1 as a diagnostic lmmunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement. Am J Surg Pathol 2012; 36: 1562-1570.
55. Anderson SE, Nonaka D, Chuai S, et al. p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas. Int J Gynecol Cancer 2006; 16: 849-853.
56. Blom R, Guerrieri C, Stal O, et al. Leiomyosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases. Gynecol Oncol 1998; 68: 54-61.
57. Hall KL, Teneriello MG, Taylor RR, et al. Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas. Gynecol Oncol 1997; 65: 330-335.
58. Konomoto T, Fukuda T, Hayashi K, et al. Leiomyosarcoma in soft tissue: examination of p53 status and cell proliferating factors in different locations. Hum Pathol 1998; 29: 74-81.
59. O’Reilly PE, Raab SS, Niemann TH, et al. p53, proliferating cell nuclear antigen, and Ki-67 expression in extrauterine leiomyosarcomas. Mod Pathol 1997; 10: 91-97.
60. Kobayashi H, Uekuri C, Akasaka J, et al. The biology of uterine sarcomas: a review and update. Mol Clin Oncol 2013; 1: 599-609.
61. Posligua L, Silva EG, Deavers MT, et al. Low-grade smooth muscle tumors of the primary and the secondary mullerian system: a proposed concept of multicentricity. Int J Gynecol Pathol 2012; 31: 547-555.
Copyright: © 2023 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2023 Termedia Sp. z o.o.
Developed by Bentus.