subject of attention objective: To evaluate the prognostic value of histopathologic variables and molecular markers in a assemblage of patients with stage I non-small small cavity lung cancer (NSCLC).

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Setting: "Maria Fetter" Hospital of Buenos Aires, Argentina.

Patients: Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999

Measurements and results: Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 528% and 28% of patients had periodical disease. We found significant differences between squamous confined apartment carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0001) and lymphatic permeation (p = 001) SCC showed higher proliferation (MIB-1 grades 2 and 3) [p = 0001] Bcl-2 expression (p = 0038) and CD44 expression (p = 0019) than adenocarcinomas. The log-rank exhibition showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to return Multivariate analysis using the Cox proportional hazards regression standard showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerg as independent prognostic factors of recurrence

Conclusions: We construct that mitosis count and MIB-1 expression had significant value to predict return reflecting the aggressiveness of high-rate proliferative tumors. We could also present to view that patients with positive Bcl-2 tumors had a poor result probably related to the uncontroll confined apartment growth that the expression of Bcl-2 aids Our observations are of potential interest for the evolution of rational postresection treatment strategies based forward the estimated risk of resort of patients with NSCLC. (CHEST 2003; 123:1858-1867)

guide words: histopathologic factors; immunohistochemistry; non-small small cavity lung cancer; prognosis; risk of recurrence; stage I

Abbreviations: NSCLC = non-small confined apartment lung cancer; SCC = squamous small cavity carcinoma; VEGF = vascular endothelial vegetation factor

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Lung cancer is the chiefly common cause of mortality to be paid to cancer worldwide. Non-small lonely dwelling lung cancer (NSCLC) accounts for approximately 80% of lung cancer. (1) Despite potential benefits of surgical resection, patients with the same pathologic stage of disease display marked variability in return and survival. Moreover, the issue after treatment in many cases has been remarkably dismal. The evolution of each individual case outcomes from the particular combination of characteristics of the patient and the tumor. The poor outcomes attained so far are at least in part, related to the high potential of NSCLC to metastasize as well as to locally be repeated These events, in turn, are not easy to predict. Better knowledge of the molecular biology of NSCLC might improve the capability to predict the issue for any individual patient, which in make go round would be helpful to define subgroup of patients for adjuvant treatment with either conventional cytotoxic chemotherapy or novel targeted agents. (2)

Tumor aggressiveness is conditioned by the agency of different biological factors that regulate, among other things, the solitary abode; squalid cycle, angiogenesis, cellular adhesion, and apoptosis. one of these factors have been evaluated to understand the way they operate and interact, and to find helpful tools to identify patients with bad prognoses. outcomes have been so far inconclusive. (2-5)

The objective of the instant study was to evaluate several histopathologic variables and a panel of molecular markers in patients with stage I NSCLC after without fault [i]or[/i] blemish [i]or[/i] flaw tumor resection to assess their prognostic value. The molecular markers analyzed in this thought encompass various biological mechanisms of tumor bourgeoning and metastases development. For a deeper examine into this complex process, we also analyzed clinical data, histopathologic observations, and molecular markers with the aid of a multivariate test

MATERIALS AND METHODS

Patients

Fifty-three patients with stage I NSCLC treated between January 1985 and December 1999 were identified from the files of the Hospital de Rehabilitacion Respiratoria "Maria Ferrer" of Buenos Aires, Argentina. Mediastinal lymph node resection was performed in all tumor staging. Inclusion criteria for note into the present study were pathologic stage IA (T1N0M0) and IB (T2NOM0) according to the revised International rule for Staging Lung Cancer, (6) radical surgery nonneoadjuvant therapy, follow-up of at least 6 month and available tissue samples for immunohistochemical study

Histopathologic Studies

sum of two units pathologists (C.P. and B.N.) independently reviewed all the histologic slides from the 53 patients in a blind fashion following the World Health Organization 1999 classification. (1) Discrepancies were solv at joint review. Pathologic features recorded included the following: tumor confined apartment type, degree of differentiation (well, moderate, and poor), tumor size (T1 up to 3 cm; T2 > 3 cm) and mitosis number in 10 high-power fields (1 up to 5; 2 6 to 10; 3 > 10) We also analyzed lymphatic tube invasion (0, absent; 1, present) vascular invasion, or tumor emboli (0 absent; 1 present) tumor necrosis (0 absent; 1 < 10%; 2 11 to 50%; and 3 > 50%) and visceral pleural invasion (0 absent; 1 present) The intensity of angiogenesis was assessed on microvessel density (microvessel defined as capillaries and small venules) in five tumor areas of maximal vascularization (400 x) identified by the agency of antibody staining to factor VIII and routine hematoxylin-eosin staining; the conclusion was displayed as the mean of the five measurements and stratified at median.

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