Mohammed Rabab A A, Makboul Rania, Elsers Dalia A H, Elsaba Tarek M A M, Thalab Abeer M A B, Shaaban Omar M
Departments of Pathology (R.A.A.M., R.M., D.A.H.E.)Obstetrics and Gynecology (O.M.S.), Faculty of Medicine, Assiut UniversityDepartment of Pathology (T.M.A.M.E.), South Egypt Cancer Institute, Assiut, EgyptDepartment of Pathology (R.A.A.M.), Faculty of Medicine, Taibah University, El-Madina Almounawwarah, Kingdom of Saudi ArabiaDepartment of Pathology (A.M.A.B.T.), Faculty of Medicine, Hadhramout University, Al Mukalla, Yemen.
Int J Gynecol Pathol. 2017 Jan;36(1):50-57. doi: 10.1097/PGP.0000000000000302.
Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant tumors (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur.
HER-2基因扩增和HER-2受体过表达在包括乳腺癌在内的多种恶性肿瘤进展中起重要作用。曲妥珠单抗(抗HER-2治疗药物)已成功用于乳腺癌治疗。本研究旨在评估一系列浆液性和黏液性卵巢肿瘤中HER-2基因扩增模式及HER-2受体表达情况,以确定这些肿瘤中HER-2是否发生与乳腺癌类似的改变。使用免疫组织化学方法用HER-2抗体对212份标本的福尔马林固定石蜡包埋微阵列组织切片进行染色,并用显色原位杂交法用抗HER-2 DNA探针进行检测。标本包括65例良性肿瘤(50例浆液性和15例黏液性)、26例交界性肿瘤(13例浆液性和13例黏液性)、73例恶性肿瘤(53例浆液性癌和20例黏液性癌)、18例转移灶(13例浆液性和5例黏液性),此外还有30例正常组织(16例卵巢表面和14例正常输卵管)。在正常或良性组织中未检测到HER-2蛋白阳性表达。交界性肿瘤显示阳性染色,但无过表达。仅在4例癌标本中观察到HER-2过表达:1/53(1.8%)原发性浆液性癌和3/20(15%)原发性黏液性癌。在4份标本中观察到HER-2基因扩增:2例原发性黏液性癌及这2例黏液性癌的2个恶性转移灶。总之,在卵巢浆液性肿瘤中未检测到HER-2改变;然而,在黏液性癌中发生了HER-2扩增和过表达。