Prognostic Significance of Tumor Infiltrating Lymphocytes in Colorectal Carcinoma Occurring in Sporadic and Familial Settings
E Vakiani, DS Klimstra, J Chou, A Weiss, M Gonen, M Weiser, J Shia. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Quantification of intraepithelial tumor infiltrating lymphocytes (TILs) on hematoxylin and eosin sections has been shown to be useful in predicting microsatellite instability (MSI) in sporadic colorectal cancer (CRC) and in hereditary nonpolyposis colorectal cancer (HNPCC). We examined the impact of the TIL count on survival, when MSI status and family history are taken into consideration.
Design: The study included 206 CRC cases from 204 patients. All cases were tested for MSI by PCR and classified as MSI-H if at least one third of the markers analyzed were abnormal. Tumors from patients who had a family history that fulfilled Amsterdam criteria or who had three or more CRC among first or second degree relatives were classified as HNPCC/HNPCC-like. The number of lymphocytes in tumor cells in 10 random high power fields (HPF) was recorded. Outcome data were obtained from the surgical database. Disease free survival (DFS) was estimated using the Kaplan-Meier method and Cox regression model was developed to determine the set of factors that independently predicted survival.
Results: The study population consisted of 101 males and 103 females (median age 62 yrs, range 23-84 yrs). Eighty cases (39%) were classified as HNPCC/HNPCC-like and 71 (34.5%) as MSI-H. The TIL count was significantly higher in MSI-H cases compared to cases with no or low MSI (57.8 vs. 9, p<0.01) and in HNPCC/HNPCC-like tumors compared to sporadic ones (42.3 vs. 15.4, p<0.01). A higher TIL count was also associated with younger age and lower tumor stage. In univariate analysis, low stage, family history and >5 TILs/10 HPF were associated with a significantly better DFS (p<0.01). The impact of MSI status on survival did not reach statistical significance (p=0.06). A high TIL count was associated with better DFS among both sporadic and familial CRC with HNPCC/HNPCC-like tumors showing >5 TILs/10 HPF having the best 5-yr DFS (95.7%). Multivariate analysis found high stage, family history and >5 TILs/10 HPF to be independent predictors of survival (hazard ratios 10.1, 0.43 and 0.4).
Conclusions: Quantification of intraepithelial TILs on hematoxylin and eosin sections provides significant prognostic information in sporadic and familial CRC independent of stage. The TIL count in our study had a greater impact on survival than MSI status and in combination with a positive family history identified a group of patients with a particularly favorable prognosis.
Tuesday, March 10, 2009 8:45 AM
Platform Session: Section C, Tuesday Morning