Histology remains the most reliable way for predicting cancer risk of premalignant (preinvasive) lesions if the OPLs show high-grade changes (i.e. severe dysplasia or carcinoma in situ, CIS): however, it is a poor predictor of the cancer risk of OPLs with no or low-grade (mild/moderate) dysplasia (termed LGOPL). It is possible that there are subtle histological differences between progressing LGOPLs and nonprogressing LGOPLs. In a recent retrospective study (Cancer Research 2008, 68:3099–107), we have shown that nuclear phenotypic score (NPS) as measured by a computer-driven microscope imaging system could serve as an adjunct tool to assist pathologists in judging the progression risk of LGOPLs Objective: to assess the potential of this new tool in identifying high-risk LGOPLs from an ongoing prospective study and to give an interim report of our results.

Methods: 284 primary LGOPLs from 284 patients were studied: 47 hyperplasias, 116 mild and 121 moderate dysplasias. Thoinin-Feulgen stained sections were imaged and analyzed to generate a NPS for each sample. The NPS was correlated with histopathology, clinical variables and outcome (progression to severe dysplasia, CIS or invasive cancer).

Results: Elevated NPS was significantly associated with progression: high NPS (≥ 4.5) was associated with a 4.7-fold increase in risk of progression as compared to low NPS (< 4.5). Of the 199 LGOPLs with low NPS, 13 (7%) progressed as compared to 26/85 (31%) of LGOPLs with high NPS (P < 0.0001). In the multivariate Cox model, high NPS was a significant risk predictor for cancer progression (P < 0.0001).

Conclusions: These data support the potential utility of automated quantitative microscopy technology to assist the pathologist in assessing progressing potential of low-grade OPLs (Supported by grant R01DE13124, NIDCR).

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A9.