Nuclear immunoreactivity of BLM-s, a proapoptotic BCL-2 family member, is specifically detected in salivary adenoid cystic carcinoma.

ABSTRACT

Tumor cells frequently evade apoptosis triggered by cellular stress via aberrant regulation of the BCL-2 family members, which are key players in regulating cell death under physiological and pathological situations. Previously, we have identified a novel BH3-only protein of the BCL-2 family, BLM-s (BCL-2-like molecule, short form), that modulates apoptosis of postmitotic immature neurons during corticohistogenesis. Whether BLM-s expression correlates with any subtype of human tumors has not been investigated. Here, via BLM-s immunohistochemistry performed in various kinds of human tumors, we demonstrate that BLM-s is specifically expressed in tumors derived from salivary gland (specificity, 0.76 [95% confidence interval, or CI], 0.65-0.85]; sensitivity, 1 [95% CI, 0.99-1]). Stratification of BLM-s immunointensity and its subcellular localization in correlation with salivary gland tumor subtype shows a statistically significant increase in proportion and in intensity of nuclear staining for adenoid cystic carcinoma (ACC; specificity, 0.92 [95% CI, 0.88-0.95]; sensitivity, 0.82 [95% CI, 0.66-0.92]), a locally aggressive head and neck malignancy. Comparison among salivary ACC in correlation with MYB/MYBL fluorescence in situ hybridization, c-KIT immunohistochemistry, and BLM-s immunohistochemistry shows that BLM-s' nuclear immunoreactivity has lower false-negative detection rate (18.5% compared with 26.3% [MYB/MYBL fluorescence in situ hybridization] and 34.2% [c-KIT], respectively). Intriguingly, ACC derived from other cell origins such as breast shows negative BLM-s immunoreactivity. We thus propose that nuclear localization of BLM-s detected by immunohistochemistry could be potentially used as an ancillary diagnostic marker for ACC originating from the salivary gland, especially when the biopsy specimen is small with an unknown tumor origin.