Gibbons M D, Manne U, Carroll W R, Peters G E, Weiss H L, Grizzle W E
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, 1501 Fifth Avenue South, Birmingham, AL 35249-6889, U.S.A.
Laryngoscope. 2001 Aug;111(8):1373-8. doi: 10.1097/00005537-200108000-00011.
OBJECTIVE/HYPOTHESIS: Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), the most common malignancies of the major salivary glands, are clinically and pathologically different. To determine whether MEC and ACC have different molecular characteristics, we examined the expression of erbB-2, erbB-3, epidermal growth factor receptor (EGFR), and transforming growth factor-alpha (TGF-alpha), important molecular features in other malignancies.
STUDY DESIGN/METHODS: Archival tissue sections of 22 MEC and 6 ACC tumors of the major salivary glands were evaluated immunohistochemically for expression of erbB-2, erbB-3, EGRF, and TGF-alpha. A differential immunostaining score, reflecting the difference in immunostaining between carcinoma and uninvolved salivary gland tissue, was calculated for cytoplasmic and membranous staining.
Positive immunostaining for all biomarkers was observed in the cytoplasm and membrane of both tumors. However, expression was higher in MEC than in ACC tumors and was statistically significant for cytoplasmic EGFR (P =.009), TGF-alpha (P =.041), and membranous EGFR (P =.004). A significantly higher percentage of MEC cells also demonstrated positive immunostaining for cytoplasmic erbB-3 (P =.022), EGFR (P =.005), membranous erbB-3 (P =.022), and EGFR (P =.013). The differential immunostaining score was significantly higher for MEC compared with uninvolved alveolar tissue and the membranes of uninvolved ductal tissue. There were no statistically positive differential immunostaining scores for ACC.
There is a clear difference in the molecular phenotypes of MEC and ACC. The lack of statistically significant expression in ACC, when compared with similar uninvolved salivary gland tissue, suggests minimal involvement for these molecular structures in the pathogenesis of ACC. Conversely, erbB-2, erbB-3, EGFR, and TGF-alpha may have a role in the development and progression of MEC. These results have therapeutic implications for MEC of the major salivary glands.
目的/假设:黏液表皮样癌(MEC)和腺样囊性癌(ACC)是大唾液腺最常见的恶性肿瘤,在临床和病理上存在差异。为了确定MEC和ACC是否具有不同的分子特征,我们检测了erbB-2、erbB-3、表皮生长因子受体(EGFR)和转化生长因子-α(TGF-α)的表达,这些是其他恶性肿瘤中的重要分子特征。
研究设计/方法:对22例大唾液腺MEC肿瘤和6例ACC肿瘤的存档组织切片进行免疫组织化学评估,以检测erbB-2、erbB-3、EGRF和TGF-α的表达。计算反映癌组织与未受累唾液腺组织免疫染色差异的差异免疫染色评分,用于细胞质和膜染色。
在两种肿瘤的细胞质和膜中均观察到所有生物标志物的阳性免疫染色。然而,MEC中的表达高于ACC肿瘤,细胞质EGFR(P = 0.009)、TGF-α(P = 0.041)和膜性EGFR(P = 0.004)的差异具有统计学意义。MEC细胞中细胞质erbB-3(P = 0.022)、EGFR(P = 0.005)、膜性erbB-3(P = 0.022)和EGFR(P = 0.013)的阳性免疫染色百分比也显著更高。与未受累的肺泡组织和未受累导管组织的膜相比,MEC的差异免疫染色评分显著更高。ACC没有统计学上的阳性差异免疫染色评分。
MEC和ACC的分子表型存在明显差异。与相似的未受累唾液腺组织相比,ACC中缺乏统计学上的显著表达,表明这些分子结构在ACC发病机制中的参与程度最小。相反,erbB-2、erbB-3、EGFR和TGF-α可能在MEC的发生和发展中起作用。这些结果对大唾液腺MEC具有治疗意义。