Immunostains Laminin-5 γ2, Kalinin B1 and αβ-Crystallin in the Evaluation of Malignant Spindle Cell Tumors of the Breast.
Dara S Ross, Timothy M D'Alfonso, Yi-Fang Liu, Stefano Monni, Sandra J Shin. Weill Cornell Medical College, New York
Background: Morphologic features of malignant mammary spindle cell tumors often overlap and immunohistochemical (IHC) stains are utilized for further characterization and diagnosis. The distinction among these entities is critical since the clinical management of these patients widely differ. In addition to cytokeratins and p63, laminin-5 γ2 (LG), kalinin B1 (i.e. laminin-5 β3) (KB) and αβ-crystallin (AB) are relatively new antibodies which are reportedly positive in the vast majority of metaplastic carcinomas. Laminin-5, consisting of the α3, β3 and γ2 chains, is a component of the basement membrane of epithelial tissues. AB is a small heat shock protein that exerts cytoprotective effects and inhibits apoptosis. We evaluated the utility of these 3 antibodies in distinguishing spindle cell metaplastic carcinomas (SMC) from other malignant mammary spindle cell tumors (MMST).
Design: 74 MMST were identified in our files (44 metaplastic carcinomas of pure or predominant spindle cell type, 14 sarcomas, 16 malignant phyllodes tumors [MPT]). IHC stains of LG (clone D4B5, Millipore), KB (clone 17, BD) and AB (clone 1B6.1-3G4, Stressgen) were performed using the Bond Max Autostainer (Leica Microsystems). For each case, LG, KB and AB was evaluated for staining intensity (negative-0, weak-1+, moderate-2+, strong-3+) and distribution (focal-25%, regional-50%, diffuse-75%) in lesional cells. Staining results were analyzed.
Results: In a given tumor, LG positivity of any intensity or distribution best separated SMC from other MMST. In our cohort, LG was positive in 31 of 44 (70%) SMC in contrast to 2 of 30 (7%) other MMST. In the majority of SMC studied, LG staining in lesional cells was diffuse (41%) or regional (23%). In the 30% of LG-negative SMC, moderate positivity for KB (i.e. at least 1+ staining in a diffuse pattern or 2+ staining in a regional pattern) identified an additional 16% of SMC cases. The LG-KB combination identified 38 of 44 (86%) of SMC studied with an overall misclassification error of 18%. Internal model validation suggests LG positivity is more accurate a classifier than the LG-KB combination. AB was the least discriminating IHC stain.
Conclusions: LG is a valuable and discriminatory IHC stain in identifying SMC from other MMST such as sarcomas and MPT. In our cohort, KB positivity in LG-negative tumors helped identify additional cases of SMC. Although validation of our findings is necessary, LG and KB are useful and should be included in the routine IHC panel employed in this diagnostic scenario.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 3, Tuesday Afternoon