Score evaluation and prevalence of Her2 status in pleural mesothelioma (PM): MESOHER study.

Abstract

e20066 Background: Tumors that overexpress HER2 have been historically associated with poorer survival compared with HER2-negative tumors. HER2 status classification has been evolving and while there are clear guidelines for breast and gastric cancers, in other tumor types have no clear guidelines. HER2 rappresents a validated target in many tumors. In this report were analyzed the HER 2 status in PM. Methods: From January 2019 to June 2024 in IRCCS-AUSL Reggio Emilia, Italy, 53 consecutive patients (pts) diagnosed with PM were analyzed examining HER2 expression by immunohistochemical (IHC) analysis and subsequent confirmation by fluorescence in situ hybridization (FISH) on diagnostic biopsies or surgical specimens. The antibody used was anti-HER-2/neu clone 4B5 (Rabbit Monoclonal Primary Antibody, Ventana). HER2 IHC was evaluated according to the 3 different HER2 Testing Guidelines for breast cancer, gastric and colorectal adenocarcinoma. Results: HER2 membrane staining was observed in 9 of 53 cases (16.9%), while 44 cases (83.1%) were completely negative. 6/9 cases was epithelioid histotype and 3/9 biphasic histotype. According to the Breast Cancer Guidelines, most cases with HER2 staining (6/9, 66.7%) were scored as 0 (Ultra-Low) with weak/barely perceptible segmental positivity in 1 to 10% of neoplastic cells (mean 3.8%); 2 cases (22.2%) were scored 1+ with weak/barely perceptible segmental positivity in 15% and 25% of neoplastic cells, respectively. In line with Gastric Adenocarcinoma Guidelines, most cases with HER2 staining (5/9, 55.6%) were scored as 1+ with weak/barely perceptible segmental positivity in 5% to 25% of neoplastic cells (average 12%); 3 cases (33.3%) were scored 0 with weak/barely perceptible segmental positivity in 1% of neoplastic cells. According to the Guidelines for adenocarcinoma of the large bowel, all cases with HER2 staining, with the exception of case 2+ (8/9, 88.9%), were found to be score 1+ with weak/barely perceptible segmental positivity in 5% to 25% of neoplastic cells (average 12%). HER2 results in the 9 PM cases showing any expression of HER2, reported according to the different guidelines currently available in clinical practice (Table1.Concordance between scores Fleiss’ Kappa 0.363). Conclusions: In this study, 16.9% of cases of PM showed any HER2 IHC membrane staining. The expression is infrequent and consistently low, affecting a small fraction of tumour cell and lacking gene amplification. HER2 results in the 9 PM cases showing any expression of HER2, reported according to the different guidelines currently available in clinical practice. Cases with any expression of HER2 HER2 Testing Guidelines Breast Cancer Gastric cancer Colorectal cancer 1 1+ 1+ 1+ 2 1+ 1+ 1+ 3 2+ 2+ 2+ 4 0 1+ 1+ 5 0 0 1+ 6 0 1+ 1+ 7 0 0 1+ 8 0 1+ 1+ 9 0 0 1+