High prognostic impact of growth fraction parameters in advanced stage laryngeal squamous cell carcinoma.

One hundred and two cases of laryngeal squamous cell carcinoma, all treated in the same center with total or supraglottic laryngectomy, bilateral neck dissection and postoperative radiotherapy, were investigated with both Ki67 and MIB-1 monoclonal antibodies. The aim was to determine the prognostic impact of growth fraction markers in a homogeneous series of patients. All samples were stained with Ki67 monoclonal antibody on frozen sections, and with MIB-1 monoclonal antibody on paraffin sections, using the ABC immunoperoxidase method. The percentage of positive cells was compared in each case with the overall and disease-free survival, pathologic stage and histologic grading. The values obtained from Ki67 and MIB-1 counts were similar and highly correlated (r=0.90). Two groups of cases with low and high proliferation rate (59 and 43 respectively) were obtained by splitting up the whole series, on the basis of the median value; 84. 6% of the patients with high proliferation relapsed and/or died due to the tumor within two years from diagnosis whereas, at time of writing, 94% of the patients with low proliferation are alive and well (p<0.00001). No relation was found between growth fraction and histologic grading, pathologic stage (pT and pN) and site of the tumor. Only lymph node involvement was correlated with disease-free survival. Our results indicate that Ki67/MIB-1 index represents an independent variable to determine long-term prognosis in laryngeal squamous cell carcinomas. We recommend its use in diagnostic protocols, to distinguish high risk subsets of patients who might benefit from more aggressive treatments.

[Laryngeal cancer and angiogenesis]. / Angiogenesi e cancro della laringe.

Angiogenesis is required for the growth of solid tumors which, in avascular condition, are limited to 2-3 mm3 volume. The switch to the angiogenic phenotype allows new vessels to converge upon the tumor, growth to proceed at an exponential rate and metastasis diffusion. The evaluation of tumoral angiogenesis has been proposed to be an independent prognostic marker of behaviour of some solid tumors: it has been demonstrated that, in some types of carcinoma (breast, prostate, lung, etc...), an intense vascular proliferation correlates with the aggressiveness of the disease. However in malignant melanomas and colorectal carcinomas, there are conflicting results on the correlation between angiogenesis and the progression of the cancer. There are also conflicting data on the role of microvessels count (MC) in the management of head and neck cancer. Despite a large number of studies, at the present, there are not biological or molecular markers available to predict consistently the outcome of the patients with laryngeal squamous cell carcinoma (LSCC). In fact the prognosis of this tumor has been mainly based, up to now, on a number of clinico-pathological parameters, especially localization, tumor extent and nodal involvement. The aim of this study has been to compare MC inside LSCC with disease free survival, grading, pT, pN and pathological stage. We investigated the relevance of the number of microvessels in the peritumoral stroma of 68 LSCC (only Caucasian males, age 35-70 years), classified according to UICC/1987 randomly selected (33 classified in clinical stage I e II and 35 in clinical stage III-IV). All patients have been surgically treated and pN + cases have been also submitted to radiotherapy. The follow-up was 60-84 months. The vascular density was assessed according to Horak et Al. with an immunohistochemical method using JC70 monoclonal antibody (CD31; Dako, Astrup, Denmark). Univariate analysis showed that MC, pT, pN, Pathological Stage and grading were correlated with the disease-free survival. A MC < 120/mm2 was predictive for a high survival index; in contrast a MC > 150 mm2 were associated with relapse. Furthermore, multivariate analysis demonstrated that MC was the only independent predictor for the disease free survival. Our findings demonstrate that in LSCC, MC is the first measurable biological parameter which is significant for evaluating the disease free-survival. Therefore, MC in LSCC is crucial in the prognosis and in the choice of a more aggressive management of the disease, including the possible treatment with antiangiogenic compound.