Xu X C, Lee J S, Lippman S M, Ro J Y, Hong W K, Lotan R
Department of Tumor Biology and Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):871-6.
Malignant transformation is often associated with alterations in the expression of normal differentiation markers, which may serve as intermediate end points in carcinogenesis and cancer prevention. To identify early changes in differentiation markers during head and neck cancer development, we examined the expression of cytokeratins (CK1, CK8, CK13, and CK19) and involucrin by immuohistochemical methods in surgical specimens from 29 head and neck squamous cell carcinoma patients that included, in addition to carcinoma, adjacent dysplastic lesions (17 cases), hyperplastic lesions (21 cases), and adjacent histologically normal tissues (15 cases) and in specimens from 31 subjects with premalignant oral lesions (e.g, oral leukoplakia) without cancer, CK13 and involucrin were detected in all specimens from the cancer patients, and no differences in their expression were found among the different histopathological group. CK8 was detected in only 2.7% (1 of 36) of adjacent normal and hyperplastic tissues but in 58.8% (10 of 17) and 75.9% (22 of 29) of dysplastic and carcinoma tissues. The corresponding figures for CK19 expression in adjacent normal, hyperplastic, dysplastic, and carcinoma tissues were 13.3, 70, 71.4, and 82.1%, respectively. The expression of CK1 was not related to the progression from normal to malignant. In the leukoplakia lesions, CK8 CK13, CK19 and involucrin were detected in 13.8, 100, 74.2 and 100% of the specimens, respectively. These results demonstrate that CK19 expression increases in hyperplastic lesions and continues to be expressed in dyplastic and malignant lesions, whereas CK8 expression in low in adjacent normal and hyperplastic tissues and increases only in dysplastic and malignant lesions. Thus, CK19 and CK8 could be markers of sequential premalignant changes in head and neck carcinogenesis.
恶性转化通常与正常分化标志物表达的改变相关，这些标志物可能作为致癌作用和癌症预防的中间终点。为了确定头颈癌发生过程中分化标志物的早期变化，我们采用免疫组织化学方法检测了29例头颈鳞状细胞癌患者手术标本中细胞角蛋白（CK1、CK8、CK13和CK19）和内披蛋白的表达，这些标本除癌组织外，还包括相邻的发育异常病变（17例）、增生性病变（21例）以及相邻的组织学正常组织（15例），同时检测了31例无癌的癌前口腔病变（如口腔白斑）患者标本中的相关指标。在癌症患者的所有标本中均检测到CK13和内披蛋白，且在不同组织病理学组中其表达无差异。CK8仅在2.7%（36例中的1例）的相邻正常和增生组织中检测到，但在发育异常和癌组织中分别有58.8%（17例中的10例）和75.9%（29例中的22例）检测到。相邻正常、增生、发育异常和癌组织中CK19表达的相应比例分别为13.3%、70%、71.4%和82.1%。CK1的表达与从正常到恶性的进展无关。在白斑病变中，CK8、CK13、CK19和内披蛋白分别在13.8%、100%、74.2%和100%的标本中检测到。这些结果表明，CK19表达在增生性病变中增加，并在发育异常和恶性病变中持续表达，而CK8在相邻正常和增生组织中表达较低，仅在发育异常和恶性病变中增加。因此，CK19和CK8可能是头颈癌发生过程中癌前连续变化的标志物。
