Carcinomas in situ of the breast with indeterminate features - Role of E-cadherin staining in categorization

Most breast carcinomas in situ (CIS) are easily categorized as ductal (DCIS ) or lobular (LCIS). However, some CIS have indeterminate histologic featur es (CIS-IF). Prior studies have shown that E-cadherin protein expression is lost in lobular but not ductal carcinomas. Therefore, evaluation of exampl es of CIS-IF for E-cadherin expression by immunohistochemistry might be use ful in helping to define their nature. To address this, we studied histolog ic features and E-cadherin expression by immunohistochemistry in 89 cases o f breast CIS (28 LCIS, 33 DCIS, 28 CIS-IF). CIS-IF cases were divided into three groups based on histology: Group 1 cases had all the cytologic and ar chitectural features typical of LCIS but showed areas of comedo-type necros is (n = 6), Group 2 cases were CIS lesions characterized by small, uniform neoplastic cells either growing in a solid pattern with focal microacinar-l ike structures but with cellular dyshesion, or growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n = 17), Group 3 ca ses showed marked cellular pleomorphism and nuclear atypia but had the dysh esive growth pattern characteristic of LCIS (n = 5). E-cadherin staining wa s scored as negative, positive, or mixed (mixture of negative and positive tumor cells). All 28 cases of LCIS were E-cadherin negative, and all 33 DCI S cases were E-cadherin positive by immunohistochemistry. All cases from CI S-IF group 1 and group 3 were negative for E-cadherin, suggesting a closer kinship to LCIS than to DCIS. In contrast, CIS-IF group 2 cases were hetero geneous with respect to E-cadherin staining. Six (35.3%) cases were E-cadhe rin negative (more akin to LCIS), 5 (29.4%) cases were E-cadherin positive (akin to DCIS), and 6 (35.3%) cases had both E-cadherin-positive and E-cadh erin-negative: tumor cells, suggesting a mixed DCIS/LCIS phenotype. Our fin dings suggest that E-cadherin immunostaining is of value in helping to char acterize breast carcinomas in situ with indeterminate features. However, va lidation of these observations will require clinical outcome studies.