title: Carcinomas in situ of the breast with indeterminate features: role of E-cadherin staining in categorization.
abstract: Most breast carcinomas in situ (CIS) are easily categorized as ductal (DCIS) or lobular (LCIS). However, some CIS have indeterminate histologic features (CIS-IF). Prior studies have shown that E-cadherin protein expression is lost in lobular but not ductal carcinomas. Therefore, evaluation of examples of CIS-IF for E-cadherin expression by immunohistochemistry might be useful in helping to define their nature. To address this, we studied histologic features and E-cadherin expression by immunohistochemistry in 89 cases of 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 architectural features typical of LCIS but showed areas of comedo-type necrosis (n = 6). Group 2 cases were CIS lesions characterized by small, uniform neoplastic cells either growing in a solid pattern with focal microacinar-like structures but with cellular dyshesion, or growing in a cohesive mosaic pattern but with occasional intracytoplasmic vacuoles (n = 17). Group 3 cases showed marked cellular pleomorphism and nuclear atypia but had the dyshesive growth pattern characteristic of LCIS (n = 5). E-cadherin staining was 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 DCIS cases were E-cadherin positive by immunohistochemistry. All cases from CIS-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 heterogeneous with respect to E-cadherin staining. Six (35.3%) cases were E-cadherin 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-cadherin-negative tumor cells, suggesting a mixed DCIS/LCIS phenotype. Our findings suggest that E-cadherin immunostaining is of value in helping to characterize breast carcinomas in situ with indeterminate features. However, validation of these observations will require clinical outcome studies.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Jacobs
authors.forename: N
authors.initials: N
authors.lastname: Pliss
authors.forename: G
authors.initials: G
authors.lastname: Kouria
authors.forename: S J
authors.initials: SJ
authors.lastname: Schnitt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification / Q000473:pathology*; D015820:Cadherins / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry / Q000145:classification / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged
chemical_list: D015820:Cadherins