Serum osteopontin levels can be used to distinguish persons with exposure to asbestos who do not have cancer from those with exposure to asbestos who have pleural mesothelioma.

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions:These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.

Purpose: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-a and ER-h and the relationship between ER status, subject characteristics, and survival. Experimental Design: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-a and ER-h expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. Results: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-a. Nuclear ER-h positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-h^positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ERh^positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-h^positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-h^negative tumors. Conclusions: This study suggests differential expression by sex and influence on survival in men of nuclear ER-h in lung cancer, particularly in adenocarcinomas.In the United States, lung cancer is the second most common cancer among both men and women and is the leading cause of cancer death in both sexes (1). A number of studies report that women are more susceptible, dose for dose, to the carcinogenic effects of cigarette smoke than men (2, 3). Women have been reported to have higher levels of polycyclic aromatic hydrocarbon-DNA adducts than men at any given level of smoking (4). Smoking females have significantly higher levels of expression of the gene encoding CYP1A1, a central enzyme in the metabolic activation of polycyclic aromatic hydrocarbons (4, 5). It has also been shown that G:C to T:A transversions in p53 are more common among females with lung cancer than males (6). One study also reported that the proportion of nonsmoking lung cancer cases in women was double that in men, suggesting that even nonsmoking women may be more susceptible to lung carcinogens than nonsmoking men (2).The reported sex difference in susceptibility suggests a role for hormones in determining lung cancer risk. Both exogenous estrogens [i.e., hormone replacement therapy (HRT) and oral contraceptives] and endogenous hormone levels (i.e., age at menopause) may contribute to the development of lung cancer (7 -10). Early age at menopause has been associated with decreased risk of adenocarci...