口腔鳞状细胞病变中Connexin43及α-SMA的表达及在鳞状细胞早期浸润癌诊断中的应用

Utility of Connexin 43 and α-SMA staining in the diagnosis of oral squamous intraepithelial lesion and the early infiltrate of oral squamous cell carcinoma

目的探讨肿瘤相关成纤维细胞(carcinoma-associated fibroblasts,CAFs)相关因子Connexin 43及α-SMA在口腔黏膜鳞状上皮病变中的表达及其在口腔鳞状细胞早期浸润癌诊断中的应用价值。方法应用免疫组化单染法(Connexin 43)及双染法(α-SMA及ERG)检测10例口腔黏膜慢性炎(chronic inflammation of oral mucosa,CIOM)、54例口腔鳞状上皮重度不典型增生(oral squamous epithelial severe dysplasia,OSESD)、58例口腔鳞状细胞原位癌(oral squamous cell carcinoma in situ,OSCCIS)、75例口腔鳞状细胞原位癌伴微浸润(oral squamous cell carcinoma in situ with micro-infiltration,OSCCISM)及口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中相应蛋白的表达,并对OSESD及OSCCIS患者进行随访,观察其疾病进展情况,分析Connexin 43及α-SMA在口腔黏膜鳞状上皮病变中表达的意义及其在口腔鳞状细胞早期浸润癌诊断中的应用价值。结果在CIOM、OSESD、OSCCIS、OSCCISM/OSCC的间质中,Connexin 43的阳性率分别为10.00%、11.11%、43.10%、61.33%,α-SMA的阳性率分别为0、9.30%、34.48%、68.00%;除CIOM与OSESD组间差异无统计学意义外,其余组间阳性率差异均有统计学意义(P<0.05);在OSCCISM/OSCC中,可明显观察到浸润癌周边的间质CAFs阳性;在OSESD及OSCCIS的随访结果显示,间质CAFs阳性患者较CAFs阴性患者更易进展为OSCC。结论间质中Connexin 43及α-SMA的阳性率随口腔鳞状上皮病变程度的增加而升高,其对一些患者的预后具有提示作用,在判断OSCCIS局部是否有浸润时,若可疑癌周边的间质呈CAFs阳性,则更支持浸润癌的诊断,因此Connexin 43及α-SMA对口腔鳞状上皮病变及鳞状细胞癌早期浸润的诊断具有一定的价值。

Purpose To certify whether the use of carcinoma-associated fibroblasts（CAFs）-related factors Connexin 43 and α-SMA in can help in the diagnosis of oral squamous intraepithelial lesion and the early invasion of oral squamous cell carcinoma. Methods The immunohistochemical single staining（Connexin 43） and double-immunostaining（α-SMA and ERG）were used in 10 cases of chronic inflammation of oral mucosa（CIOM）,54 oral squamous epithelial severe dysplasia（OSESD）,58 oral squamous cell carcinoma in situ（OSCCIS）,and75 oral squamous cell carcinoma in situ with micro-invasion（OSCCISM） and oral squamous cell carcinoma（OSCC） to detect the expression of Connexin 43 and α-SMA protein,and patients with OSESD and OSCCIS were followed up and the prognosis of the patients was observed to analyze the value of Connexin43 and α-SMA protein in judging the progress of oral squamous intraepithelial lesion and the early invasion of oral squamous cell carcinoma. Results In single staining sections,the expression of Connexin 43 in CIOM,OSESD,OSCCIS,and OSCCISM/OSCC was 10. 00%,11. 11%,43. 10% and 61. 33%,respectively,while the results of α-SMA expressed in these cases were 0. 00,9. 30%,34. 48% and 68. 00%,respectively,in doublestaining sections. Among them,there was no significant difference between CIOM and OSESD,but the differences between the other three groups were statistically significant（P〈0. 05）.In cases of OSCCISM,obviously positive expression of CAFs was observed in the surrounding stroma of invasive carcinoma. In the follow-up results of OSESD and OSCCIS,we found that patients with positive expression of CAFs were more likely to progress to OSCC than those patients that showed negative. Conclusion The expression of Connexin 43 and α-SMA is increased from OSESD to OSCC,which suggests the prognosis of some patients. It will support the diagnosis of OSCCISM if the surrounding stroma of the suspected cancer shows positive expression of CAFs.Therefore,Connexin 43 and α-SMA may be useful to help diagnoses of oral squamous intraepithelial lesion and the early invasion of OSCC.