Overexpression of the p53 Tumor Suppressor Gene Product in Primary Lung Adenocarcinomas Is Associated with Cigarette Smoking

Westra, William H.; Offerhaus, G.J.A.; Goodman, Steve; Slebos, Robbert J.C.; Polak, M.; Baas, Inge O.; Rodenhuis, S.; Hruban, Ralph H.

doi:10.1097/00000478-199303000-00001

Cited by 86 publications

(34 citation statements)

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“…The compiled data from the two groups indicate that, on average, more than half of the patients who continued smoking, less than 40% of those who had stopped smoking before clinical diagnosis, and less than 30% of those who were nonsmokers had a p53 mutation. A previous study on lung adenocarcinoma found an increasing proportion of patients with p53 overexpression in current smokers versus former smokers versus nonsmokers (56% vs 33% vs 0%) (15). These observations of a decreased frequency of p53 alterations in former smokers and nonsmokers, as contrasted to smokers, appear to be consistent with the epidemiological data pointing to a clear beneficial effect of stopping smoking, as seen in cancer mortality for most primary sites including the lung and bladder (16).…”

Section: Discussionsupporting

confidence: 85%

Cigarette smoking and p53 mutations in lung cancer and bladder cancer.

Husgafvel‐Pursiainen

Kannio

1996

Environ Health Perspect

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We report here a compilation of p53 mutation results from two smoking-related cancers, lung cancer and bladder cancer. The overall mutation frequencies reported for these two types of cancer were relatively similar-50% in lung cancer and 40% in bladder cancer. The compiled data from lung cancer and bladder cancer suggest an increasing proportion of patients with p53 mutations in nonsmokers, former smokers, and current smokers, in that order, in both cancer groups. Taken together, more than half (55% and 56% for lung cancer and bladder cancer, respectively) of the patients who continued smoking (CS), less than 40% (38% and 38%) of those who had stopped smoking before (.1 or .5 years) clinical diagnosis (ES), and less than 30% (25% and 29%) of those who were nonsmokers (NS) had a p53 mutation. The differences seen in the mutation frequencies between the three smoking groups did not, however, reach statistical significance (lung cancer-CS vs ES: odds ratio [OR] = 2.0, 95% Cl 0.7-5.4; CS vs NS: OR=3.7, 95% Cl 0.4-37; bladder cancer-CS vs ES: OR=2.1, 95% Cl 0.6-7.9; CS vs NS: OR=3.1, 95% Cl 0.7-13). Guanine to thymine transversions were the most common type in lung cancer followed by guanine to adenine transitions. In bladder cancer, on the contrary, G:C to A:T transitions at cytosine-guanine dinucleotide sites were the most frequently detected base substitutions. Analysis of the compiled p53 mutation data suggests that, in addition to lifetime cumulative exposure to cigarette smoke, also stopping smoking for years prior to clinical manifestation of the disease may affect the incidence of p53 mutations. The differences in the mutation profiles appear to support the view that the main genotoxic agents from cigarette smoke exposure may be different in bladder cancer as compared to lung cancer, as suggested previously by DNA adduct studies. Environ Health Perspect 104(Suppl 3): 553-556 (1996)

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Section: Discussionsupporting

confidence: 85%

Cigarette smoking and p53 mutations in lung cancer and bladder cancer.

Husgafvel‐Pursiainen

Kannio

1996

Environ Health Perspect

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“…Histological features suggesting malignancy included: the presence of monotonous mucinous cells that were cuboidal or columnar and lacked cilia, the absence of squamous metaplasia, the formation of papillary projections and crowded growth, and the presence of significant atypia. In addition, P53 protein was consistently expressed in all histological patterns and especially by cells lining these pseudobronchiolar formations, in agreement with the P53 accumulation observed in 30% of pulmonary adenocarcinoma and 66% of nonsmall cell lung carcinoma [4,5]. However, such a P53 accumulation can also be detected in several nontumoral conditions, such as diffuse alveolar damage, as a reactive process leading to alveolar cell apoptosis regardless of a gene alteration [6].…”

Section: Discussionsupporting

confidence: 61%

Adenocarcinoma of the lung mimicking inflammatory lung disease with honeycombing

Lantuéjoul

Colby²,

Ferretti

et al. 2004

European Respiratory Journal

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Pulmonary adenocarcinoma of the lung and its variants are well-defined entities, since the recent WHO classification of lung tumours. However, scant descriptions have been allocated to associated stromal changes, such as prominent inflammation and fibrosis, which can overshadow a tumoral proliferation and masquerade as a benign reactive process and this has not been recognised as a histopathological variant.The case of a 72-yr-old farmer who presented a multifocal well-differentiated adenocarcinoma that mimicked honeycomb lung with bronchiolectasis radiologically, on computed tomography scan and histologically at open lung biopsy, is reported. Histological pitfalls in the biopsy were represented by mild atypical cuboidal or columnar epithelial cells lining bronchiolar structures resembling florid bronchiolar metaplasia in a background of extensive fibrosis and inflammation, features that mimicked inflammatory honeycombing. However, histological analysis of the surgical resection of the main lesion, performed because of a clinical alteration of the patient, confirmed the diagnosis of multifocal adenocarcinoma of mixed subtype. A monomorphic proliferation of clear cells, lack of associated ciliated or squamous cells and presence of significant cytologic atypia gave a diagnosis of malignancy.This case illustrates how inflammatory and fibrotic changes may conceal a correct diagnosis of carcinoma and emphasises the importance of adequate sampling in such cases. Eur Respir J 2004; 24: 502-505.

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“…23 Abnormalities in p53 expression has been documented in pulmonary adenocarcinomas, [24][25][26] and it has been suggested that increased labeling of tumor cells with p53 is associated with a poor prognosis. 9,12,25 Of the tumors analyzed for p53 staining, those in groups III and IV had higher positive labeling for the marker than the other two groups, although in our study, the difference is not statistical significant.…”

Section: Prognostic Factormentioning

confidence: 99%

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

et al. 2007

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This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and r5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and 45 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm þ pure invasive groups (groups III, IV), and the o5 mm þ noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma. Noguchi et al 2 looked at small lung adenocarcinomas measuring o2 cm, and defined six different categories including pure bronchioloalveolar carcinoma, bronchioloalveolar carcinoma with areas of fibroblastic foci due to structural collapse, bronchioloalveolar carcinoma with active fibroblastic proliferation, and different categories of invasive carcinoma. They showed that patients with tumors with a pure bronchioloalveolar carcinoma pattern had a 100% 5-year survival, patients with adenocarcinomas of mixed subtype with bronchioloalveolar carcinoma and invasive components had a 75% 5-year survival, while those patients with a purely invasive carcinoma had a 52% 5-year survival.

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Overexpression of the p53 Tumor Suppressor Gene Product in Primary Lung Adenocarcinomas Is Associated with Cigarette Smoking

Cited by 86 publications

References 0 publications

Cigarette smoking and p53 mutations in lung cancer and bladder cancer.

Cigarette smoking and p53 mutations in lung cancer and bladder cancer.

Adenocarcinoma of the lung mimicking inflammatory lung disease with honeycombing

Histologic features are important prognostic indicators in early stages lung adenocarcinomas

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