Correlation of Twist Expression in Primary Non Small Cell Lung Carcinomas with Histologic Subtypes, Risk of Metastases, and Overall Patient Survival.
Katherine Downey, Yanelba Toribio, Hasmeena Kathuria, Benedict Daly, Carl O'Hara. Boston Medical Center, MA
Background: Literature suggests metastasis involves the activity of Twist, a highly conserved basic helix-loop-helix transcription factor that down-regulates E-cadherin expression, allowing epithelial-to-mesenchymal transition (EMT). It is believed EMT allows carcinoma cells to disseminate to distant organs. Twist over-expression has been shown to be an independent marker in predicting metastatic risk and overall prognoses in various cancer types (i.e. melanoma, breast carcinoma, ovarian, and prostate cancer). To our knowledge, Twist expression in NSCL carcinomas has not been well studied. The goal of our study is to assess Twist expression in adenocarcinoma primary lung tumors of varying degrees of differentiation and different histological subtypes, and correlate this with metastasis risk and patient prognosis.
Design: Monoclonal Twist antibody was used to stain sections of primary tumor of resected lung cancer cases in which permission was granted for research purposes.. Twist staining was graded (0-3+) based on an average of positive nuclear stained cells per six 40X fields (0: no staining, 1+: 1-75, 2+ 76-150, 3+ >150). Counts were performed blindly as to TNM status, histologic subtype, and patient survival time.
Results: ANOVA analysis proved significant difference between histologic subtypes (p<0.05) and degrees of differentiation in adenocarcinomas (p<0.05). Appropriately, bronchoalveolar carcinoma subtype showed absent Twist staining. Significant difference of Twist expression was observed between low and high T-stage cases (p<0.03). Twist over-expression was observed in tumors with positive node metastasis compared to tumors without (p = 0.07). Kaplan Meier survival curve showed strong correlation with high Twist expression and low overall survival, and low expression with good prognosis.
Conclusions: In agreement with recent studies stating prognoses varies with histologic subtypes, our data shows significant difference in Twist expression amongst corresponding subtypes. Significant difference in Twist expression was noted in poorly differentiated adenocarcinomas, as compared to moderately and well-differentiated forms. Twist was found to be over-expressed in tumors with nodal involvement compared to those without. In conclusion, our findings suggest that high Twist expression is an independent marker in NSCLC prognosis, and can be useful in risk stratification and tailoring therapeutic modalities.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 225, Monday Morning