Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?

karabağ, sevil

doi:10.4274/jarem.galenos.2021.3974

Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?

Sevil KARABAĞ (Tekirdağ Namık Kemal Üniversitesi, Tıp Fakültesi, Patoloji Anabilim Dalı, Tekirdağ, Türkiye)

JAREM

0 0

Yıl: 2021 Cilt: 11 Sayı: 1 Sayfa Aralığı: 32 - 37 Metin Dili: İngilizce DOI: 10.4274/jarem.galenos.2021.3974 İndeks Tarihi: 04-12-2021

Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?

Öz:

Objective: Endometrial carcinoma (EC) is a highly heterogeneous malignancy in terms of morphology, clinical course, response to treatment and prognosis. This study aimed to investigate the loss of INI1 (SWI/SNF family member) and E-cadherin expression in type 1 and 2 ECs to elucidate the mechanisms that may elucidate on the differences in pathogenesis and prognosis between low- and high-grade histological types. Methods: Immunohistochemistry (IHC) was applied for INI1 and E-cadherin in 72 patients who underwent hysterectomy for EC. Loss of INI1 and E-cadherin expression was compared between subjects with low- and high-grade EC. Results: A total of 63 patients had type 1 (endometrioid) and nine had type 2 (non-endometrioid) tumours. IHC staining revealed loss of INI1 expression in eight cases. While three of these cases were serous carcinoma, three were endometrioid carcinoma with villoglandular pattern and two were grade 3 endometrioid carcinoma. A significant difference was found in the loss of INI1 expression between low-grade (G1-G2) and highgrade (G3 endometrioid carcinoma and non-endometrioid carcinoma) tumours (p=0.004). Loss of expression was observed only in one case of dedifferentiated carcinoma in IHC staining performed for E-cadherin in 72 cases. Conclusion: A significantly greater loss of INI1 expression was observed in high-grade compared with low-grade endometrial carcinoma. This finding confirms that INI1 loss is a poor prognostic factor in these tumours as in other tumours reported in the literature and sheds light on the different pathogeneses seen in high-grade EC. To the best of our knowledge, this is the first systematic study to investigate INI1 loss in different types of endometrial carcinoma. Our results support the notion that SWI/SNF chromatin remodelling complex plays a role in the pathogenesis of high-grade EC and type 1 endometrioid carcinoma with villoglandular pattern.

Anahtar Kelime:

Endometrial Karsinomlarda INI1 ve E-kadherin Ekspresyon Kaybının Önemi Var Mı?

Öz:

Amaç: Endometriyal karsinomlar (EK), morfoloji, klinik seyir, tedaviye yanıt ve prognoz açısından oldukça heterojen malignitelerdir. Bu çalışmada, düşük ve yüksek dereceli EK histolojik tipleri arasındaki patogenez ve prognozdaki farklılıklara ışık tutabilecek mekanizmaları aydınlatmak için tip 1 ve 2 EK’de INI1(SWI/SNF ailesi üyesi) ve E-kaderin ekspresyon kaybını araştırmayı amaçlamaktadır. Yöntemler: EK tanısıyla histerektomi yapılan 72 hastaya ait tümör dokularına INI1 ve E-kaderin immünohistokimya (IHK) boyamaları uygulandı. Düşük ve yüksek dereceli EK’li hastalar arasında INI1 ve E-kaderin ekspresyon kaybı karşılaştırıldı. Bulgular: Yetmiş iki hastanın 63’ü tip 1 (endometrioid) tümör ve 9’u tip 2 (endometrioid olmayan) karsinom tipindeydi. IHK boyama, sekiz olguda INI1 ekspresyonunda kayıp olduğunu gösterdi. Bu olguların üçü seröz karsinom iken, üçü villoglandüler paternli endometrioid karsinom ve ikisi grade 3 endometrioid karsinomdu. Düşük dereceli (G1-G2) ve yüksek dereceli (G3 endometrioid karsinom ve endometrioid-olmayan karsinomlar) tümörler arasında INI1 ekspresyon kaybı açısından istatistiksel olarak anlamlı fark saptandı (p=0,004). E-kadherin kaybı yalnızca dediferansiye karsinom tanılı bir olguda gözlendi. Sonuç: Yüksek dereceli EK’ler, düşük dereceliler ile karşılaştırıldığında INI1 ekspresyonunda anlamlı ölçüde kayıp gözlendi. Bu bulgu, INI1 kaybının, literatürde diğer tümörler için bildirilen olgularda olduğu gibi, EK’lerde kötü prognostik faktör olduğunu doğrulamakta ve yüksek dereceli EK’de görülen farklı patogeneze ışık tutmaktadır. Bildiğimiz kadarıyla çalışmamız farklı EK tiplerinde INI1 kaybını araştıran ilk sistematik çalışmadır. Sonuçlarımız, SWI/SNF kromatin yeniden şekillenme kompleksinin, yüksek dereceli EK ve villoglandüler paternli tip 1 endometrioid karsinomun patogenezinde rol oynadığını desteklemektedir

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, SanzPamplona R. Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol 2017; 145: 200-7.
2. Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, et al. Endometrial carcinoma: molecular alterations involved in tumor development and progression, Oncogene 2013; 32: 403-13.
3. Kurman RJ, Carcangiu ML, Herrington CS, Young RH. WHO classification of tumors of the female reproductive organs. WHO classification of tumors. Lyon: IARC Press; 2014.
4. Hamilton CA, Cheung MK, Osann L, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer 2006; 94: 642-6.
5. Matias-Guiu X, Prat J. Molecular pathology of endometrial carcinoma, Histopathology 2013; 62: 111-23.
6. Esteller M, Garcia A, Martinez-Palones J, Xercavins J, Reventos J. Clinicopathologic features and genetic alterations in endometrioid carcinoma off the uterus with villoglandular differentiation. Am J Clin Pathol 1999; 111: 336-42.
7. Ambros RA, Ballouk F, Malfetano JH, Ross JS. Significance of papillary (villoglandular) differentiation in endometrioid carcinoma of the uterus. Am Surg Pathol 1994; 18: 557-69.
8. Strehl JD, Wachter DL, Fiedler J, Heimerl E, Beckmann MW, Hartmann A, et al. Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant. Ann Diagn Pathol 2015; 19: 198-202.
9. Wang X, Haswell JR, Roberts CW. Molecular pathways: SWI/SNF (BAF) complexes are frequently mutated in cancer-mechanisms and potential therapeutic insights. Clin Cancer Res 2014; 20: 21-7.
10. Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS One 2013; 81: e55119.
11. Judkins AR. Immunohistochemistry of INI1 expression: a new tool for old challenges in CNS and soft tissue pathology. Adv Anat Pathol 2007; 14: 335-9.
12. Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 2011; 35: 47-63.
13. Forrest SJ, Al-Ibraheemi A, Doan D, Ward A, Clinton CM, Putra J, et al. Genomic and immunologic characterization of INI1-deficient pediatric cancers. Clin Cancer Res 2020; 26: 2882-90.
14. Tang SJ, Zhai CW, Yuan CC, Zhang JH, Wang SY. SMARCB1 (INI1)- deficient sinonasal carcinoma: a clinicopathological analysis of six cases. Zhonghua Bing Li Xue Za Zhi 2020; 49: 47-51.
15. Florescu MM, Pırıcı D, Sımıonescu CE, Stepan AE, Mărgărıtescu C, Tudorache S, et al. E-cadherin and β-catenin immunoexpression in endometrioid endometrial carcinoma. Rom J Morphol Embryol 2016; 571: 1235-40.
16. Xiong S, Klausen C, Cheng JC, Leung PCK. Activin B promotes endometrial cancer cell migration by downregulating E-cadherin via SMAD-independent MEK-ERK1/2-SNAIL signaling. Oncotarget, 2016; 28: 40060-72.
17. Wong SHM, Fang CM, Chuah LH, Leong CO, Ngai SC. E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol 2018; 121: 11-22.
18. Costa LC, Leite CF, Cardoso SV, Loyola AM, Faria PR, Souza PE, et al. Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma. J Appl Oral Sci 2015; 23: 169-78.
19. Choi JE, Bae JS, Kang MJ, Chung MJ, Jang KY, Park HS, et al. Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: clinicopathological significance. Oncol Rep 2017; 38: 1695-705.
20. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 2013; 31: 2607-18.
21. Rubeša-Mihaljevic R, Babarovic E, Vrdoljak-Mozetic D, StembergerPapic S, Klaric M, Krasevic M, et al. The immunohistochemical pattern of epithelial-mesenchymal transition markers in endometrial carcinoma. Appl Immunohistochem Mol Morphol 2019; 53: 164-72.
22. Youssef MY, Mohamed MA. Could e-cadherin and cd10 expression be used to differentiate between atypical endometrial hyperplasia and endometrial carcinoma? Appl Immunohistochem Mol Morphol 2019; 38: 128-37.
23. Jie D, Zhongmin Z, Guoqing L, Sheng L, Yi Z, Jing W, et al. Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer. Dig Dis Sci 2013; 58: 1581-9.
24. Zhang L, Kwan SY, Wong KK, Soliman PT, Lu KH, Mok SC. pathogenesis and clinical management of uterine serous carcinoma. Cancers(Basel) 2020; 12: 686.
25. Bi R, Yu L, Tu XY, Ge HJ, Cheng YF, Chang B, et al. Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features]. Zhonghua Bing Li Xue Za Zhi 2019; 8: 590-5.
26. Abro B, Kaushal M, Chen L, Wu R, Dehner LP, Pfeifer JD, et al. Tumor mutation burden, DNA mismatch repair status and checkpoint immunotherapy markers in primary and relapsed malignant rhabdoid tumors. Pathol Res Pract 2019; 215 :152395.
27. Vroobel KM, Attygalle AD. Sarcomatous Transformation in Undifferentiated/ Dedifferentiated Endometrial Carcinoma: An Underrecognized Phenomenon and Diagnostic Pitfall. Int J Gynecol Pathol 2020; 39: 485-92.

APA	karabağ s (2021). Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. , 32 - 37. 10.4274/jarem.galenos.2021.3974
Chicago	karabağ sevil Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. (2021): 32 - 37. 10.4274/jarem.galenos.2021.3974
MLA	karabağ sevil Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. , 2021, ss.32 - 37. 10.4274/jarem.galenos.2021.3974
AMA	karabağ s Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. . 2021; 32 - 37. 10.4274/jarem.galenos.2021.3974
Vancouver	karabağ s Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. . 2021; 32 - 37. 10.4274/jarem.galenos.2021.3974
IEEE	karabağ s "Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?." , ss.32 - 37, 2021. 10.4274/jarem.galenos.2021.3974
ISNAD	karabağ, sevil. "Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?". (2021), 32-37. https://doi.org/10.4274/jarem.galenos.2021.3974

APA	karabağ s (2021). Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. JAREM, 11(1), 32 - 37. 10.4274/jarem.galenos.2021.3974
Chicago	karabağ sevil Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. JAREM 11, no.1 (2021): 32 - 37. 10.4274/jarem.galenos.2021.3974
MLA	karabağ sevil Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. JAREM, vol.11, no.1, 2021, ss.32 - 37. 10.4274/jarem.galenos.2021.3974
AMA	karabağ s Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. JAREM. 2021; 11(1): 32 - 37. 10.4274/jarem.galenos.2021.3974
Vancouver	karabağ s Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?. JAREM. 2021; 11(1): 32 - 37. 10.4274/jarem.galenos.2021.3974
IEEE	karabağ s "Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?." JAREM, 11, ss.32 - 37, 2021. 10.4274/jarem.galenos.2021.3974
ISNAD	karabağ, sevil. "Do INI1 and E-cadherin Expression Loss Have Any Significance in Endometrial Carcinomas?". JAREM 11/1 (2021), 32-37. https://doi.org/10.4274/jarem.galenos.2021.3974