High level of nucleolar expression of catalytic subunit of human telomerase reverse transcriptase (hTERT) is associated with better prognosis in patients with esophageal and esophagogastric junction adenocarcinomas

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 5672 Background: Telomerase, a ribonucleoprotein that maintains telomers, is composed of the catalyticprotein subunit (hTERT) and a telomerase RNA template. Recent studies have shown that nucleolar expression of hTERT is a prognostic marker for several malignancies including gastrointestinal cancers. The expression of hTERT and its prognostic significance in esophageal and esophagogastric junction (EGJ) adenocarcinomas has not been studied in detail. In this study, we examined the expression of hTERT in 94 esophageal and EGJ adenocarcinoma and correlated expression with clinicopathologic features and prognosis. Design: We constructed tissue microarrays using formalin-fixed, paraffin-embedded archival tissue from 94 consecutive patients from 1986 through 1998 at MD Anderson Cancer Center who had undergone esophagectomy for clinically localized esophageal and EGJ adenocarinomas (8 stage I, 20 stage II, 49 stage III, 17 stage IV). Each tumor was sampled in triplicate with a 1-mm punch core. The expression levels of hTERT were evaluated by immunohistochemistry with a mouse anti-hTERT monoclonal antibody (Clone 44F12, 1:25, Novacastra, Novwel, MA). The staining results were scored quantitatively using Ariol Image Analysis System (San Jose, CA). The tumor cells were marked with a handdraw tool and the hTERT nucleolar labeling index in tumor cells was measured as a ratio between the stained nucleolar area and the total nuclear area of tumor cells. The computerized images and results were reviewed by two gastrointestinal pathologists. Statistical analyses were performed using SPSS software (version 12.0; SPSS, Chicago, IL) and survival was evaluated by Cox regression analysis. Result: High level of nucleolar expression of hTERT (hTERT-high, defined by labeling index of >10%) was present in 33 of 94 (35%) tumors. Patients with hTERT-high tumors had better recurrence-free survival (p=0.017), overall survival (p=0.013), and less frequent distant metastasis (p=0.04) than patients with hTERT-low tumors in univariate analysis. In multivariate analysis, tumors with hTERT-high (p=0.046 and p=0.038), pN stage (p=0.001 and p=0.001) and the number of positive lymph nodes (p=0.006 and p=0.009) significantly correlated with recurrence-free and overall survival respectively, independent of T stage and M status. Conclusion: Our results indicate that high level of nucleolar expression of hTERT was present in a subset of esophageal and EGJ adenocarcinoma and was an independent prognostic factor for better overall and recurrence-free survivals.