Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing ...of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic lesions, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.
We describe herein the reduction in the size of an ACTH-secreting pituitary macroadenoma in a patient with Nelson's syndrome during chronic administration of sodium valproate, and the changes in ...tumour volume after withdrawal and re-institution of treatment. The patient had elevated plasma ACTH levels (1123-1255 pmol/l), which increased markedly after CRH stimulation. A first 4-month course of sodium valproate administration (600 mg/day, orally) was started. Plasma ACTH fell to 550-726 pmol/l with persistence of responsiveness to CRH; brain computed tomography showed a clearcut reduction of tumour size. One month after drug withdrawal, the tumour volume appeared unchanged and plasma ACTH values ranged between 374 and 440 pmol/l. One and a half year after drug withdrawal, a brain computed tomography showed re-expansion of the pituitary adenoma with evidence of suprasellar extension, which had never been seen previously. Plasma ACTH ranged between 113 and 199 pmol/l. A second course of sodium valproate was started; after three months, a brain computed tomography documented clearcut reduction of tumour volume from a suprasellar extension to a partially empty pituitary fossa. Plasma ACTH ranged from 396 to 542 pmol/l with persistence of responsiveness to CRH. The present report documents for the first time the reduction of tumour size in a patient with an ACTH-secreting macroadenoma by chronic administration of sodium valproate.
Background: Tumors acquire nutrients that are essential for continued growth and an avenue for dissemination to the rest of the body by inducing angiogenesis (i.e., the formation of new blood ...vessels). Preliminary studies involving a number of different kinds of cancer have indicated that an assessment of tumor angiogenesis may be useful in predicting disease outcome. Purpose: In a prospective study, we evaluated the relationship between tumor angiogenesis and survival for 407 patients with nonsmall- cell lung carcinoma who were treated with potentially curative surgery. Methods: The study population consisted of 360 male and 47 female patients who underwent surgery consecutively at the Department of Surgery, University of Pisa, Italy, from March 1991 through December 1994. Followup lasted through February 1996, with a median follow-up for living patients of 29 months (range, 15-60 months). An anti-CD34 monoclonal antibody, which is specific for endothelial cells, and standard immunohistochemical techniques were used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel counts; the counts for single, highpower microscopic fields (magnification ×250) in the three most intense areas of blood vessel growth for each sample were averaged. The median microvessel count in this series was 20, and the counts were categorized as follows: 1) low versus high (⩽20 versus >20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31-40, and ⩾41 microvessels). Disease-free and overall survival during follow-up were assessed. Kaplan-Meier survival curves were modeled in a univariate analysis of patient and tumor characteristics; the Cox proportional hazards model was used in multivariate analysis. Reported P values are two-sided. Results and Conclusions: In the univariate analysis, patients with larger tumors (P for trend <.00001), a more advanced tumor stage (P for trend <.00001), a greater degree of regional lymph node involvement (P for trend <.00001), or more vascularized tumors (high versus low microvessel count, P<.00001) experienced significantly reduced overall survival. When microvessel counts were analyzed in five categories, a highly significant trend (P<.00001) toward worse prognosis was observed with increasing tumor vascularity. In multivariate analysis, tumor microvessel count (P<.00001), tumor size (P = .0006), and regional lymph node status (P<.00001) retained independent prognostic value with respect to overall survival; among these variables, tumor microvessel count, considered as a continuous variable, was the most important, with a relative hazard of death of 8.38 (95% confidence interval = 4.19- 16.78) associated with the highest microvessel counts. Implications: An evaluation of tumor angiogenesis may be useful in the postsurgical staging of patients with non-small-cell lung carcinoma and in identifying subsets of patients who may benefit from different postsurgical treatments.
The importance of evaluating receptors for estrogen and progestin in human breast cancer has been pointed out by many authors. In the absence of a reference standard, receptor assays must be ...controlled by intra and interlaboratory quality control programs. Much interlaboratory variability exists due to non-uniform analytical protocols, non-uniform ligands, intrinsic errors and also errors in computation methods. The goals of our Italian Quality Control Program on Multicenter Trials are to standardize the analytical procedures and computation methods. Twenty Italian laboratories participated in the Quality Control Program. Each specimen was assayed for steroid receptor content according to the standardized dextran-coated-charcoal method. Data were subjected to computerized analyses by 5 different methods of calculation (Scatchard plot, direct plot, Lineweaver-Burk method, Brunauer-Emmet-Teller analysis, single-point approach). The results were than evaluated to identify intra- and inter-assay variation coefficients and to define other statistical parameters. The authors suggest different calculation methods depending on the specific experimental and/or physiopathological conditions.
Since 1979 the quality control design proposed by the Italian ad hoc Committee has evaluated several lyophilized preparations with scalar receptor content; this permits the identification by linear ...regression analysis of systematic and non systematic errors. At present 41 laboratories from most of the national regions have joined the Italian Committee. The overall results of five years application of quality assurance in Italy show that there was a different pattern of imprecision with satisfactory indexes for intralaboratory performances but major variations in interlaboratory controls. There was also a remarkable difference of variability indices between the so-called "expert" and "new" laboratories; this problem can be reduced with practical seminars for new centers. On the basis of the results and experience achieved the Committee is starting another program of quality assurance for different new methodologies to provide guidelines for international working reference standards.
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