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Ann Thorac Surg 2004;77:1883-1890
© 2004 The Society of Thoracic Surgeons
a Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil
b Department of Thoracic Surgery, University of São Paulo Medical School, São Paulo, Brazil
c Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Accepted for publication November 25, 2003.
* Address reprint requests to Dr Capelozzi, Department of Pathology, School of Medicine, University of São Paulo, Av. Dr. Arnaldo 455, 01246-903, São Paulo SP, Brazil
e-mail: vcapelozzi{at}lim05.fm.usp.br
BACKGROUND: Because biological behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and angiogenesis, p21waf1/cip1 and microvessel density have been targeted as potentially useful tumor markers. We sought to validate the importance of p21waf1/cip1 and microvessel density and study their interrelationship, analyzing clinical factors, subclassifications, and tumor and stromal markers.
METHODS: We examined p21waf1/cip1 and other markers in tissue from 61 patients with surgically excised large cell carcinomas. The amount of tumor staining for p21waf1/cip1 and microvessel density was evaluated by immunohistochemistry and morphometry. The study outcome was survival time until death from recurrent lung cancer.
RESULTS: Multivariate Cox model analysis demonstrated that after surgical excision, histologic subtypes were significantly related to survival time (p = 0.02), but quantitative staining of the tumor for p21waf1/cip1 and microvessel density added prognostic information and these variables were more strongly prognostic than histologic subtype (p = 0.00). Cut points at the median staining of 3.5% and 3.0% for p21waf1/cip1 and microvessel density, respectively, divided patients into two groups with distinctive survival times. Patients with p21waf1/cip1 staining of more than 3.5% and microvessel density staining of more than 3.0% had a median survival time of 14 months.
CONCLUSIONS: Tumor staining for p21waf1/cip1 and microvessel density in resected large cell carcinomas and certain other types of lung tumors was strongly related to survival. Patients with more than 3.0% staining in their tumors were at high risk of death from lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.
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