Survival analyses and immunohistochemical study of primary signet ring cell carcinoma of the lung adenocarcinoma

Chunji Chen, Lei Wang, Chang Gu, Yiyang Wang, Xufeng Pan, Shijie Fu, Jun Yang, Rui Wang


Background: The clinicopathological features, immunohistochemical (IHC) characteristics and survival outcomes of primary lung adenocarcinoma with signet ring cells (LAdSRCs) component were analyzed.
Methods: A retrospective analysis of primary LAdSRCs consecutively collected from 2010 to 2014 was performed and compared with lung adenocarcinoma (ADC). We investigated the survival outcomes and the expression of cytokeratin 7 (CK7), CK20, thyroid transcription factor-1 (TTF-1) and villin in these 35 cases of primary LAdSRCs.
Results: We identified 1,715 patients in total, 35 (2.0%) of whom had signet ring cell (SRC) component. Excepting for 2 cases without IHC information, a CK profile (CK7+/CK20–) were identified in 69.7% (23/33) of LAdSRC; 22 (66.7%) of 33 LAdSRCs exhibited positive TTF-1 expression, but no other TTF-1 positive was found in signet ring cell carcinoma (SRCC) of other organs, and villin was not identified in these 33 cases. Age, sex, tumor size, surgery resection, smoking history, tumor stage, nodal stage, predominant histology subtype, pathology and adjuvant therapy were all significant predictors of relapse-free survival (RFS) and overall survival (OS) in univariable analysis. Compared to lung ADC, the lung ADCs with SRC component had an inferior prognosis. In multivariable analysis, sex, tumor size, tumor stage, nodal stage, predominant histology subtype and adjuvant therapy were still significant predictors for both RFS and OS while the pathology [RFS: hazard ratio (HR), 0.918; 95% confidence interval (CI), 0.581–1.492; P=0.712; OS: HR, 1.392; 95% CI, 0.820–2.364; P=0.221, respectively] was not.
Conclusions: Univariable analysis revealed primary LAdSRC is a rare ADC subtype with a worse prognosis compared with ADC. The high percentage expression of TTF-1 and immunostaining profiles CK7+/CK20- in primary LAdSRC is significant to identify the source of SRCCs.