IDENTIFICATION OF MOLECULAR MARKERS IN DCIS RECURRENCE

Abstract

Background: DCIS represents preinvasive malignant change. With screening mammography DCIS has become a common entity. Its natural history is poorly understood and treatment remains controversial. Using a retrospective population based cohort, we have identified histological and molecular variables predictive of recurrence.Methods: All cases of DCIS reported in Victoria between 1988 and 1992 were entered into the Victorian Cancer Registry. In Situ and Small Cancer Register (ISSIBCR) and followed up annually regarding treatment, the event of recurrence and its nature and location. From this register a cohort of 66 DCIS lesions with subsequent recurrence as in situ or invasive disease were studied histologically, immunohistochemically and with CGH‐based genetic analyses comparing them to a nested randomized control group of DCIS without recurrence matched for patient age and year of diagnosis. Recurrences have been analysed by the same techniques to compare them to the primary lesion.Results: 13 histological features were evaluated and lesion size, nuclear pleomorphism, cellular polarity, micropapillary architecture and central necrosis were all significant predictors of recurrence (p < 0.05). Immunohistochemistry showed p21 overexpression, bcl2 negativity and ERBB2 positivity to be markers of recurrence. In the case of ERBB2, positivity was a predictor of recurrence even when its overexpression was focal. Primary and recurrent DCIS lesions had similar morphological appearances, and grade of primary DCIS correlated with grade of subsequent invasive cancer. This morphological similarity was paralleled by similar protein expression and genomic changes in both in situ and invasive recurrences.Conclusion: We have identified histological and immunohistochemical markers of recurrence in DCIS, and shown similarities in morphology, protein expression and genetic changes between primary DCIS and its recurrence.