BACKGROUND: Trastuzumab in association with systemic cytotoxic chemotherapy is the standard of care for patients with advanced HER2-positive gastric carcinoma (GC). However, HER2 as a prognostic factor in GC remains controversial. METHODS: HER2 overexpression and amplification was evaluated by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 2,798 GCs obtained from 2,727 gastrectomy and 71 open/laparoscopic biopsy specimens from patients with peritoneal seeding. Regional heterogeneity was defined as the proportion of tumor cells showing membranous staining in 10-70 % of tumor cells. Genetic heterogeneity was determined by the existence of HER2/CEP17 ratio higher than 2.0 in >5 to <50 % of tumor cells. RESULTS: In IHC, 184 cases (6.6 %) were 3+ and 44 cases (1.6 %) were 2+. Of 44 HER2 2+ cases, SISH showed HER2 gene amplification in 21 cases (47.7 %), chromosome 17 polysomy in six cases (13.6 %), and genetic heterogeneity in five cases (11.4 %). HER2 positivity found in 7.3 % of GCs was significantly associated with older age, male gender, intestinal histology, upper third in location, higher lymph node stage (p < .002), and advanced AJCC stage (p = .033). Regional heterogeneity of HER2 was closely associated with 2+ (70.5 vs 42.9 % in 3+, p = .001) and diffuse or mixed histologic type (p = .005). CONCLUSIONS: Regional heterogeneity of HER2 expression was closely associated with weak HER2 overexpression (2+) and with diffuse or mixed histology. Polysomy of chromosome 17 would be an important cause of HER2 2+ in IHC. Frequent HER2 positivity observed in GCs with advanced stages suggests that HER2 may be involved in tumor progression and poor prognosis.
BACKGROUND:Trastuzumab in association with systemic cytotoxic chemotherapy is the standard of care for patients with advanced HER2-positive gastric carcinoma (GC). However, HER2 as a prognostic factor in GC remains controversial. METHODS:HER2 overexpression and amplification was evaluated by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 2,798 GCs obtained from 2,727 gastrectomy and 71 open/laparoscopic biopsy specimens from patients with peritoneal seeding. Regional heterogeneity was defined as the proportion of tumor cells showing membranous staining in 10-70 % of tumor cells. Genetic heterogeneity was determined by the existence of HER2/CEP17 ratio higher than 2.0 in >5 to <50 % of tumor cells. RESULTS: In IHC, 184 cases (6.6 %) were 3+ and 44 cases (1.6 %) were 2+. Of 44 HER2 2+ cases, SISH showed HER2 gene amplification in 21 cases (47.7 %), chromosome 17 polysomy in six cases (13.6 %), and genetic heterogeneity in five cases (11.4 %). HER2 positivity found in 7.3 % of GCs was significantly associated with older age, male gender, intestinal histology, upper third in location, higher lymph node stage (p < .002), and advanced AJCC stage (p = .033). Regional heterogeneity of HER2 was closely associated with 2+ (70.5 vs 42.9 % in 3+, p = .001) and diffuse or mixed histologic type (p = .005). CONCLUSIONS: Regional heterogeneity of HER2 expression was closely associated with weak HER2 overexpression (2+) and with diffuse or mixed histology. Polysomy of chromosome 17 would be an important cause of HER2 2+ in IHC. Frequent HER2 positivity observed in GCs with advanced stages suggests that HER2 may be involved in tumor progression and poor prognosis.
Authors: Zhe-Ling Chen; Andi Zhao; Pan Li; Mi Zhang; Jiao Yang; Lingxiao Zhang; Xiaoai Zhao; Jin Yang; Le Wang Journal: Oncol Lett Date: 2018-07-25 Impact factor: 2.967
Authors: Angela N Bartley; Mary Kay Washington; Christina B Ventura; Nofisat Ismaila; Carol Colasacco; Al B Benson; Alfredo Carrato; Margaret L Gulley; Dhanpat Jain; Sanjay Kakar; Helen J Mackay; Catherine Streutker; Laura Tang; Megan Troxell; Jaffer A Ajani Journal: Am J Clin Pathol Date: 2016-11-14 Impact factor: 2.493
Authors: Pietro Achilli; William Perry; Fabian Grass; Mohamed A Abd El Aziz; Scott R Kelley; David W Larson; Kevin T Behm Journal: Updates Surg Date: 2021-05-15
Authors: Soomin Ahn; Mineui Hong; Michael Van Vrancken; You Jeong Lyou; Seung Tae Kim; Se Hoon Park; Won Ki Kang; Young Suk Park; Sin-Ho Jung; Minah Woo; Jeeyun Lee; Kyoung-Mee Kim Journal: Mol Diagn Ther Date: 2016-08 Impact factor: 4.074