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Histopathological Features of HER2 Overexpression in Uterine Carcinosarcoma: Proposal for Requirements in HER2 Testing for Targeted Therapy

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Journal Virchows Arch
Date 2021 Jan 10
PMID 33423127
Citations 7
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Abstract

Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealed HER2 gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells.

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References
1.
Pradhan T, Stevens E, Ablavsky M, Salame G, Lee Y, Abulafia O . FIGO staging for carcinosarcoma: can the revised staging system predict overall survival?. Gynecol Oncol. 2011; 123(2):221-4. DOI: 10.1016/j.ygyno.2011.08.007. View

2.
Fujii H, Yoshida M, Gong Z, Matsumoto T, Hamano Y, Fukunaga M . Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity. Cancer Res. 2000; 60(1):114-20. View

3.
Zhao S, Bellone S, Lopez S, Thakral D, Schwab C, English D . Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition. Proc Natl Acad Sci U S A. 2016; 113(43):12238-12243. PMC: 5087050. DOI: 10.1073/pnas.1614120113. View

4.
Yamada S, Burger R, Brewster W, Anton D, Kohler M, Monk B . Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus. Cancer. 2000; 88(12):2782-6. DOI: 10.1002/1097-0142(20000615)88:12<2782::aid-cncr17>3.0.co;2-k. View

5.
Ferguson S, Tornos C, Hummer A, Barakat R, Soslow R . Prognostic features of surgical stage I uterine carcinosarcoma. Am J Surg Pathol. 2007; 31(11):1653-61. DOI: 10.1097/PAS.0b013e3181161ba3. View