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Epidermal growth factor receptor (EGFR) is a transmembrane protein receptor with tyrosine kinase activity. The protein has cysteine-rich sequence repeats in its extracellular ligand-binding domains. Elevated levels of EGFR are associated with malignant transformation of squamous cells and are observed in squamous cell carcinomas from the lung, head, neck, skin, cervix and esophagus. We examined the expression of EGFR in laryngeal squamous cell carcinoma (SCC) (N = 24) and non-neoplastic polyps (N = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody (Serotec: MCA-571) to the EGFR protein. The carcinomas were classified as well differentiated (N = 2), moderately differentiated (N = 16) and poorly differentiated (N = 6). Tissues from metastatic tumor deposits in lymph nodes (N = 5) were also studied. Overexpression of EGFR was present, in the form of strong cytoplasmic immunostaining, in the majority of the SCC cases (n = 20; 83%) and in all of the metastatic tumor deposits. In contrast, although some of the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunoreactivity, none had evidence of strong EGFR immunoreactivity. The differences in EGFR immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test), and between metastatic laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test). Laryngeal carcinoma cases which showed EGFR overexpression had a lower median survival period compared to those without overexpression In conclusion, a different extent of EGFR expression is demonstrated in laryngeal squamous cell carcinomas and non-neoplastic vocal cord polyps using an immunohistochemical method. Some trends in the prognostic value of EGFR immunoreactivity in laryngeal carcinomas appear to emerge in this study.

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BACKGROUND: Transforming growth factor alpha (TGF-alpha) is a polypeptide that is structurally similar to epidermal growth factor (EGF) that binds to the epidermal growth factor receptor (EGFR) and has been implicated in the development of several types of human tumours. METHODS: The expression of TGF-alpha is examined in laryngeal squamous cell carcinoma (SCC) (n = 24) and non-neoplastic polyps (n = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody to the TGF-alpha protein. These cases had been previously characterized for EGFR immunoreactivity. The carcinomas were classified as well differentiated (n = 2), moderately differentiated (n = 16) and poorly differentiated (n = 6). Tissues from metastatic tumour deposits in lymph nodes (n = 5) were also studied. RESULTS: TGF-alpha overexpression was defined as intense immunoreactivity in more than two-thirds of tumour cells immunostained for TGF-alpha and was present in the majority of the SCC cases (n = 15; 63%) and metastatic tumour deposits (n = 4; 80%). In contrast, although some of the vocal cord polyps showed weak (n = 2) to moderate (n = 5) immunostaining, none had evidence of strong TGF-alpha immunoreactivity. The differences in TGF-alpha immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (P = 0.013; chi 2 test with continuity correction), and between metastatic laryngeal SCC and vocal cord polyps (P = 0.023; chi 2 test with continuity correction). There was no significant difference in TGF-alpha expression between the different grades of carcinomas (P = 0.92, chi 2 test) or between non-metastatic and metastatic carcinomas (P = 0.82; chi 2 test with continuity correction). No significant correlation was found between TGF-alpha expression and patient survival or tumour recurrence (r = 0.077, r2 = 0.006, P = 0.75; simple regression analysis), or between TGF-alpha expression and EGFR immunoreactivity (r = 0.325, r2 = 0.106, P = 0.0851). CONCLUSIONS: In conclusion, increased TGF-alpha immunoreactivity is present in most cases of laryngeal SCC with no specific relationship to tumour grade, suggesting that it may be important in the development of laryngeal carcinomas but not in its progression. No significant correlation was found between TGF-alpha and EGFR expression in laryngeal tumours and TGF-alpha immunoreactivity is of no prognostic value.

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BACKGROUND: The nm23-H1 gene encodes a 17-kilodalton cytoplasmic and nuclear protein that has recently been shown to be reduced in a number of human carcinomas including breast, colorectal, lung, gallbladder, and biliary tract carcinomas. This study examines the immunohistochemical staining characteristics of the nm23-H1 protein in human laryngeal carcinomas and nonneoplastic laryngeal polyps, and attempts to determine if there is any relationship between reduction of nm23-H1 protein immunoreactivity and prognosis of patients with laryngeal carcinoma. METHODS: Routine streptavidin-biotin immunohistochemistry with a polyclonal antibody was employed to study the expression of the nm23-H1 protein in laryngeal squamous cell carcinoma (SCC) (N = 22) and nonneoplastic polyps (N = 8). The carcinomas were classified as well differentiated (N = 2), moderately differentiated (N =15), and poorly differentiated (N = 5). Tissues from metastatic tumor deposits in lymph nodes (N = 5) were also studied. A semiquantitative immunostaining index was derived from the intensity and extent of staining of the cells. RESULTS: All laryngeal polyps showed intense immunostaining for the nm23-H1 gene product in the squamous epithelium. However, reduced immunoreactivity was found in nearly half of the SCC cases (N = 10; 46%), with the least staining intensity found in tumor metastases in lymph nodes (N = 4; 80%), and were associated with a shorter median survival of 14.3 months. In contrast, tumors that demonstrated moderate to strong nm23-H1 protein immunostaining were associated with a longer median survival period of 20.4 months. CONCLUSIONS: There is reduced expression of the nm23-H1 gene in human laryngeal SCC compared with nonneoplastic laryngeal polyps. Reduction in the intensity and extent of nm23-H1 protein immunostaining appears to correspond to reduced duration of patients survival.

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Abnormal patterns of expression of the basement membrane type IV collagen are observed in many human cancers. This study examines the immunohistological expression of type IV collagen in the basement membrane in human laryngeal squamous cell carcinomas (SCC) (n = 24). Non-neoplastic vocal cord polyps (n = 4) were used as controls. The formalin-fixed, paraffin-embedded tissues were sectioned and pretreated with protease prior to immunostaining for type IV collagen. There was a statistically significant difference in type IV collagen expression between laryngeal SCC and vocal cord polyps (p = 0.0001; chi 2 test with continuity correction). In laryngeal SCC (n = 24; 100%), type IV collagen distribution was discontinuous and irregular or absent around individual or groups of neoplastic cells. In contrast, all of the cases of vocal cord polyps (n = 4; 100%) displayed a continuous pattern of subepithelial basement membrane type IV collagen. This study has shown that abnormal distribution of type IV collagen occurs in laryngeal squamous cell carcinomas but not in non-neoplastic vocal cord polyps. This may be related to either abnormal synthesis or to the breakdown of the collagen and it may be of use as a potential biological marker in the study of laryngeal carcinogenesis.

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