Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination.

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.