Yu C J, Shun C T, Yang P C, Lee Y C, Shew J Y, Kuo S H, Luh K T
Department of Internal Medicine, College of Medicine, National Taiwan University, Republic of China.
Am J Respir Crit Care Med. 1997 Apr;155(4):1419-27. doi: 10.1164/ajrccm.155.4.9105088.
Mucin production, when heavily sialylated, can promote cancer cell invasion and metastasis, and modulate the immune recognition system of the host. To explore the prognostic implication of sialomucin expression in lung cancer, we studied 116 patients with non-small-cell lung cancer (NSCLC). Tumor specimens were stained immunohistochemically with monoclonal antibodies (mAbs) against mucin glycoprotein (17Q2, HMFG2, SM3), and histochemically with periodic acid-Schiff/alcian blue to differentiate neutral mucin from acid mucin, and with high-iron diamine/alcian blue to differentiate sialomucin from sulfomucin. The expression status of two established molecular prognostic factors, the p53 and erbB-2 oncoproteins, were evaluated immunohistochemically. The staining was performed on two separately archived, paraffin-embedded tumor blocks for each patient, with normal lung as a control. Correlations were subsequently made among stains and various clinicopathologic factors. All analyses were blinded, and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Associations were established among adenocarcinoma histotype and erbB-2 overexpression, sialomucin expression, and 17Q2 and HMFG2 immunohistochemical positivity (p < 0.05). Sialomucin expression was closely linked to erbB-2 overexpression (p = 0.01). Significant univariate predictors (p < 0.05) of recurrence and cancer death were surgical stage, p53 expression, erbB-2 overexpression, and sialomucin expression. These four factors remained as independent predictors of early recurrence (p < 0.05) after multivariate analysis. For cancer death prediction, p53 and sialomucin expression had a marginal effect. We concluded that sialomucin expression is also a poor indicator of prognosis, which is associated with erbB-2 oncoprotein overexpression, early postoperative recurrence, and cancer death in NSCLC.
当黏蛋白产生高度唾液酸化时,可促进癌细胞侵袭和转移,并调节宿主的免疫识别系统。为了探究唾液酸化黏蛋白表达在肺癌中的预后意义,我们研究了116例非小细胞肺癌(NSCLC)患者。肿瘤标本用抗黏蛋白糖蛋白的单克隆抗体(mAb,17Q2、HMFG2、SM3)进行免疫组织化学染色,并用高碘酸-希夫/阿尔辛蓝进行组织化学染色以区分中性黏蛋白和酸性黏蛋白,用高铁二胺/阿尔辛蓝区分唾液酸化黏蛋白和硫酸化黏蛋白。免疫组织化学评估了两个已确定的分子预后因素p53和erbB-2癌蛋白的表达状态。对每位患者的两个单独存档的石蜡包埋肿瘤块进行染色,并以正常肺组织作为对照。随后对染色结果与各种临床病理因素进行相关性分析。所有分析均采用盲法,包括Kaplan-Meier生存估计和Cox比例风险回归建模。腺癌组织学类型与erbB-2过表达、唾液酸化黏蛋白表达以及17Q2和HMFG2免疫组织化学阳性之间存在关联(p<0.05)。唾液酸化黏蛋白表达与erbB-2过表达密切相关(p = 0.01)。复发和癌症死亡的显著单因素预测指标(p<0.05)为手术分期、p53表达、erbB-2过表达和唾液酸化黏蛋白表达。多因素分析后,这四个因素仍是早期复发的独立预测指标(p<0.05)。对于癌症死亡预测,p53和唾液酸化黏蛋白表达有边际效应。我们得出结论:唾液酸化黏蛋白表达也是一个不良预后指标,与NSCLC中erbB-2癌蛋白过表达、术后早期复发和癌症死亡相关。