PURPOSE: Bronchial carcinogenesis is a multistep process characterized by accumulation of genetic and @entity74 , which precedes and accompanies the preinvasive lesions known as @entity1141 and @entity2735 ( @entity2735 ). We hypothesized that the level of accumulated @entity74 in @entity1141 assessed by immunohistochemical markers might reflect the severity of the carcinogenic process, thus allowing for risk assessment in smokers. EXPERIMENTAL DESIGN: We performed a prospective analysis of bronchial biopsies in 48 former smokers who had at least one area of @entity4648 . Twenty-two of the @entity1 had a previous history of @entity2 . Eighty @entity2488 were recorded at baseline, including 31 @entity4648 , 12 mild @entity1141 , 9 moderate @entity1141 , 9 severe @entity1141 , and 19 CISs. Forty-one percent of the @entity1 had multiple preinvasive lesions. Immunohistochemical analysis of @entity876 , @entity4910 , cyclin E, @entity589 , and @entity588 was performed. Aberrant expression of one of these proteins as compared with normal bronchi was recorded as one molecular alteration. RESULTS: After 18 months, 17 @entity1 were diagnosed with @entity2 . No isolated parameter, including @entity6349 grade or any isolated molecular alteration, was significantly associated with @entity5 occurrence at 18 months follow-up, using a logistic regression statistical analysis. In contrast, considering @entity2735 and @entity5 as end point, more than two immunohistochemical abnormalities were associated with @entity5 or @entity2735 occurrence (P = 0.02). CONCLUSIONS: We concluded that the cumulative index of immunohistochemical abnormalities in a random @entity1141 is associated with @entity5 in the cancerization field of symptomatic smokers, independently of the histopathological grade of @entity1141 . This set of histopathological biomarkers might be useful in risk assessment and provide intermediate end points for chemopreventive trials.

Value of immunohistochemical markers in preinvasive @entity2488 in risk assessment of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity589 :: ('581', 'Gene') :: ['Bax'] @entity588 :: ('596', 'Gene') :: ['Bcl2'] @entity2735 :: ('MESH:D002278', 'Disease') :: ['CIS', 'carcinoma in situ'] @entity2488 :: ('MESH:D001982', 'Disease') :: ['bronchial lesions'] @entity5 :: ('MESH:D009369', 'Disease') :: ['CIS or lung cancer', 'cancer'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity4910 :: ('595', 'Gene') :: ['cyclin D1'] @entity876 :: ('7157', 'Gene') :: ['P53'] @entity4648 :: ('MESH:D008679', 'Disease') :: ['metaplasia'] @entity74 :: ('MESH:D030342', 'Disease') :: ['molecular abnormalities'] @entity6349 :: ('MESH:D004416', 'Disease') :: ['dysplastic'] @entity1141 :: ('MESH:C535662', 'Disease') :: ['dysplasia']
@entity2 :: (MESH:D008175,Disease) :: ['lung cancer']
