Weed Donald T, Gomez-Fernandez Carmen, Yasin Mohammed, Hamilton-Nelson Kara, Rodriguez Michael, Zhang Jin, Carraway Kermit L
Department of Otolaryngology, University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida 33136, USA.
Laryngoscope. 2004 Aug;114(8 Pt 2 Suppl 101):1-32. doi: 10.1097/00005537-200408001-00001.
OBJECTIVES/HYPOTHESIS: Expression of the membrane mucin MUC4 has been associated with a variety of malignancies, including squamous cell carcinoma of the upper aerodigestive tract. MUC4 modulates cell signaling pathways as an intramembrane ligand of ErbB2. The hypotheses of the study were that MUC4 expression would correlate with ErbB2 expression and that MUC4 expression would correlate with clinical outcomes in squamous cell carcinoma of the upper aerodigestive tract.
Retrospective chart review was combined with immunohistochemical analysis of paraffin-embedded tumor specimens from patients treated with initial definitive surgical resection at an academic tertiary care medical center.
MUC4 and ErbB2 receptor expression was localized by immunohistochemical studies using archival formalin-fixed and paraffin-embedded tissue. A limited number of fresh-frozen tissues were further analyzed by Western blot. Clinical outcomes and histopathological parameters were determined by retrospective chart review and correlated with immunohistochemical findings.
One hundred fifty-four patients were analyzed with a median follow-up of 12 months among 54 patients who died and 49 months among 100 surviving patients. Membrane expression of MUC4 and ErbB2 was seen in 12% and 13% of tumors, respectively. MUC4 expression was not correlated with pathological grade. A significant correlation was found between MUC4 expression and ErbB2 expression. Multivariate survival analyses revealed that patients whose tumors exhibited MUC4 membrane expression had statistically significant improvement in survival and longer time to recurrence compared with patients whose tumors did not express MUC4 as defined by immunohistochemical staining patterns. No correlations between ErbB2 expression and survival or recurrence were observed.
Patients with tumors that retain MUC4 expression exhibit improved survival and decreased recurrence in squamous cell carcinoma of the upper aerodigestive tract. Correlations between MUC4 expression patterns and ErbB2 expression are also observed, suggesting that MUC4-ErbB2 mediated cell signaling pathways may provide insights into this clinical result.
目的/假设：膜黏蛋白MUC4的表达与多种恶性肿瘤相关，包括上消化道鳞状细胞癌。MUC4作为ErbB2的膜内配体调节细胞信号通路。本研究的假设是，MUC4表达与ErbB2表达相关，且MUC4表达与上消化道鳞状细胞癌的临床结局相关。
回顾性病历审查与免疫组织化学分析相结合，对在一所学术性三级医疗中心接受初次确定性手术切除治疗的患者的石蜡包埋肿瘤标本进行分析。
使用存档的福尔马林固定石蜡包埋组织，通过免疫组织化学研究定位MUC4和ErbB2受体的表达。通过蛋白质印迹法对有限数量的新鲜冷冻组织进行进一步分析。通过回顾性病历审查确定临床结局和组织病理学参数，并与免疫组织化学结果相关联。
对154例患者进行了分析，54例死亡患者的中位随访时间为12个月，100例存活患者的中位随访时间为49个月。分别在12%和13%的肿瘤中观察到MUC4和ErbB2的膜表达。MUC4表达与病理分级无关。发现MUC4表达与ErbB2表达之间存在显著相关性。多变量生存分析显示，与免疫组织化学染色模式定义的肿瘤未表达MUC4的患者相比，肿瘤表现出MUC4膜表达的患者在生存率和复发时间方面有统计学意义的改善。未观察到ErbB2表达与生存或复发之间的相关性。
在上消化道鳞状细胞癌中，肿瘤保留MUC4表达的患者生存率提高，复发率降低。还观察到MUC4表达模式与ErbB2表达之间的相关性，这表明MUC4-ErbB2介导的细胞信号通路可能为这一临床结果提供见解。
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