Saurabh Animesh, Raphael Vandana, Dey Biswajit, Harris Caleb, Jagtap Vikas, Das Umesh
Department of Pathology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, 793018 India.
Department of Surgical Oncology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, India.
Indian J Surg Oncol. 2021 Apr;12(Suppl 1):144-151. doi: 10.1007/s13193-020-01245-w. Epub 2020 Oct 16.
The process of tumorigenesis in gastric carcinoma involves multiple genetic alterations including overexpression of PD-L1, amplification of Her2neu, and mutation of p53. In the present study, the expressions of PD-L1 and Her2neu were analyzed in relation to clinicopathological parameters including p53 in gastric and gastroesophageal junction adenocarcinoma. We examined 100 biopsy and resection samples of gastric and gastroesophageal junction carcinomas for PD-L1, Her2neu, and p53 protein expressions using immunohistochemistry. Scorings were done based on intensity and percentage of tumor cells expressing the markers. Follow-up and survival analyses were done wherever data was available. PD-L1 and Her2neu were seen in 37% and 38% respectively. The analysis showed PD-L1 expression was significantly associated with depth of invasion ( = 0.0007), nodal metastasis ( = 0.0003), and AJCC staging ( = 0.0085). Her2neu negative including equivocal expression was significantly associated with histological grading ( = 0.0043), Lauren classification ( = 0.0042), depth of invasion ( = 0.04), and nodal metastasis ( = 0.017). Combined analysis of PD-L1 and Her2neu showed significant association with histological grading ( = 0.017), Lauren classification ( = 0.005), depth of invasion ( = 0.0035), and nodal metastasis ( = 0.00073). Univariate Cox regression analysis showed that depth of invasion, nodal metastasis, distant metastasis, AJCC staging, and p53 were negative prognostic factors for patients' overall survival. In multivariate analysis, distant metastasis and Her2neu negativity including equivocal cases were independent prognostic factors. PD-L1 positivity was seen in cases with advanced pathological features, which suggest its role in the tumorigenesis of gastric and gastroesophageal junction adenocarcinoma. Her2neu positivity showed no correlation with advanced pathological features as well as no prognostic significance, which could be attributed to tumor heterogeneity, endoscopic nature of the biopsies, and non-confirmation of equivocal cases by fluorescent in situ hybridization.
胃癌的肿瘤发生过程涉及多种基因改变，包括PD-L1的过表达、Her2neu的扩增以及p53的突变。在本研究中，分析了PD-L1和Her2neu的表达与胃和胃食管交界腺癌的临床病理参数（包括p53）之间的关系。我们使用免疫组织化学检查了100例胃和胃食管交界癌的活检及切除样本中的PD-L1、Her2neu和p53蛋白表达。根据表达标志物的肿瘤细胞的强度和百分比进行评分。 wherever data was available（此句有误，应是wherever data was available，直译为“只要有数据可用的地方”，这里意译为“有数据的情况下”）进行随访和生存分析。PD-L1和Her2neu的表达率分别为37%和38%。分析表明，PD-L1表达与浸润深度（P = 0.0007）、淋巴结转移（P = 0.0003）和AJCC分期（P = 0.0085）显著相关。Her2neu阴性（包括可疑表达）与组织学分级（P = 0.0043）、Lauren分类（P = 0.0042）、浸润深度（P = 0.04）和淋巴结转移（P = 0.017）显著相关。PD-L1和Her2neu的联合分析显示与组织学分级（P = 0.017）、Lauren分类（P = 0.005）、浸润深度（P = 0.0035）和淋巴结转移（P = 0.00073）显著相关。单因素Cox回归分析显示，浸润深度、淋巴结转移、远处转移、AJCC分期和p53是患者总生存的负性预后因素。多因素分析中，远处转移和Her2neu阴性（包括可疑病例）是独立的预后因素。PD-L1阳性见于具有晚期病理特征的病例，这表明其在胃和胃食管交界腺癌的肿瘤发生中起作用。Her2neu阳性与晚期病理特征无相关性，也无预后意义，这可能归因于肿瘤异质性、活检的内镜性质以及荧光原位杂交对可疑病例的未确认。
