Ramdial P K, Madaree A, Reddy R, Chetty R
Department of Pathology, Faculty of Medicine, University of Natal, Durban, South Africa.
J Cutan Pathol. 2000 Jul;27(6):283-91. doi: 10.1034/j.1600-0560.2000.027006283.x.
bcl-2, the well known anti-apoptotic gene, cloned more than a decade ago, promotes cell viability without promoting cell proliferation. With few exceptions, high bcl-2 protein expression is associated with a favourable outcome in epithelial tumours. bcl-2 immunoreactivity in basal cell carcinomas (BCCs) is contradictory, with 67-100% immunopositivity being reported. Although BCCs are traditionally regarded as low-grade, indolent tumours, aggressive BCCs (A-BCCs) are mutilative, locally destructive tumours that often recur. bcl-2 protein expression as a predictor of BCC aggressiveness is poorly documented in the English-language literature. The bcl-2 protein immunoprofile of 50 clinically non-aggressive (NA-BCCs) and 25 clinically A-BCCs was investigated. Of the latter, 17 manifested with one, two or three recurrences. bcl-2 protein expression in each of the recurrences was also evaluated. bcl-2 expression was scored as follows: 0-5% positive cells=negative, 6-25%=1+, 26-50%=2+, 51-75%=3+, >75%=4+. "High" labeling encompassed 3+ or 4+ labeling while "low" labeling referred to 1 + or 2 + labeling. Although bcl-2 positivity was noted in all BCCs, low bcl-2 labeling was a statistically significant feature of A-BCCs (p < 0.01). High bcl-2 labeling of NA-BCCs was a reflection of the bcl-2 labeling of the dominant constituent nodular or superficial subtypes. Micronodular BCCs revealed 2+ or 3+ labeling. Initial and recurrent A-BCCs with a pure or predominantly infiltrative component, demonstrated 1+ or 2+ bcl-2 labeling. The differential bcl-2 expression in the various clinicopathological subtypes of BCCs suggests that, despite the common derivation of these tumours from a primitive basaloid stem cell and a limited potential for metastasis, they form a heterogeneous group of tumours that differ markedly in histologic and biological behaviour. While the superficial and nodular BCCs are indolent slow-growing tumours with high bcl-2 labeling, the aggressive BCCs are infiltrative, desmoplastic tumours with low bcl-2 labeling. In mixed tumours, heterogeneity of labeling is a distinctive feature and is contributed to in part by the labeling trends of the different histological subtypes. The micronodular BCC shows varied bcl-2 labeling but in combined tumours occupies a niche intermediate between the non-aggressive nodular and superficial and the aggressive infiltrative subtypes. The initial and subsequent biopsies of recurrent, adequately excised BCCs share a pure or mixed, predominantly infiltrative, stroma-rich histomorphology with low bcl-2 labeling, reflecting the immunoprofile of a more aggressive growth pattern.
bcl-2是一种著名的抗凋亡基因，于十多年前被克隆出来，它可促进细胞存活但不促进细胞增殖。除少数例外情况外，上皮性肿瘤中bcl-2蛋白高表达与良好预后相关。基底细胞癌（BCC）中bcl-2免疫反应性存在矛盾，报告的免疫阳性率为67%至100%。尽管传统上BCC被视为低级别、生长缓慢的肿瘤，但侵袭性基底细胞癌（A-BCC）具有毁容性、局部破坏性，且常复发。bcl-2蛋白表达作为BCC侵袭性的预测指标在英文文献中记载较少。对50例临床非侵袭性基底细胞癌（NA-BCC）和25例临床侵袭性基底细胞癌进行了bcl-2蛋白免疫表型研究。在后者中，17例出现了一次、两次或三次复发。还评估了每次复发时bcl-2蛋白的表达情况。bcl-2表达评分如下：0 - 5%阳性细胞为阴性，6 - 25%为1 +，26 - 50%为2 +，51 - 75%为3 +，>75%为4 +。“高”标记包括3 +或4 +标记，而“低”标记指1 +或2 +标记。尽管在所有基底细胞癌中均发现bcl-2阳性，但低bcl-2标记是侵袭性基底细胞癌的一个具有统计学意义的特征（p < 0.01）。NA-BCC的高bcl-2标记反映了主要成分结节型或浅表型的bcl-2标记情况。微结节型基底细胞癌显示2 +或3 +标记。具有纯或主要为浸润性成分的初发和复发性A-BCC显示1 +或2 +的bcl-2标记。基底细胞癌不同临床病理亚型中bcl-2表达的差异表明，尽管这些肿瘤均起源于原始基底样干细胞且转移潜能有限，但它们构成了一组异质性肿瘤，在组织学和生物学行为上有显著差异。浅表型和结节型基底细胞癌是生长缓慢的惰性肿瘤，bcl-2标记高，而侵袭性基底细胞癌是浸润性、促纤维增生性肿瘤，bcl-2标记低。在混合性肿瘤中，标记的异质性是一个显著特征，部分是由不同组织学亚型的标记趋势所致。微结节型基底细胞癌的bcl-2标记各不相同，但在混合性肿瘤中占据了介于非侵袭性结节型和浅表型与侵袭性浸润型之间的位置。复发性、切除充分的基底细胞癌的初次和后续活检标本具有纯或混合、主要为浸润性、富含基质的组织形态学特征，bcl-2标记低，反映了更具侵袭性生长模式的免疫表型。
