HER-2/neu has no role in melanogenesis. Both c-Kit (expressed in superficial spreading disease) and VEGF (expressed in amelanotic melanoma) may have significant therapeutic implications as molecular targets, which warrants further investigation.
Prediction of outcome in patients with meningiomas remains a significant problem to date. We have evaluated the role of symptoms at presentation and overexpression of her-2/neu overexpression as independent prognostic factors in meningiomas. In a retrospective study on patients with biopsy-proven diagnosis of meningioma, her-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or =2+ was considered positive for overexpression. Two hundred thirty-seven patients thus identified between January 1986 and December 1999 included 149 females and 88 males, with a mean age of 63.44 years. Survival was estimated using the Kaplan-Meier method. Incidence of meningiomas in females (62.8%) was significantly greater than in males. Focal neurodeficits, headache, and seizures (39.66%) were the most common presenting complaints and were not related to tumor behavior/outcome. Syncope at presentation was associated with a decreased survival, but this symptom constituted only 2.53% of the total, so reliable conclusions could not be drawn. Only 6 (2.53%) specimens revealed HER-2/neu overexpression by IHC. HER-2/neu overexpression is not a predictor of tumor behavior and has no role as a prognostic factor in meningiomas. Syncope as the clinical presentation at diagnosis may predict a poor outcome, but needs further investigation.
Evidence implicating pesticides as causative agents of prostate cancer is controversial, and specifically, data in young adults is lacking. Hence, we performed a preliminary study evaluating the relationship between pesticide exposure and prostate cancer in young males. After approval from the University of North Dakota Institutional Review Board and Human Subjects Committee, a retrospective study was performed on all young males ( = 50 years) with a biopsy-proven diagnosis of carcinoma of the prostate. The records of all patients aged less than/equal to 50 years, with a diagnosis of adenocarcinoma of the prostate, from January 1991 through December 2001 were reviewed. Pesticide risk assessment interviews were performed by a single member of the team, for consistency, via telephone on the basis of a pre-determined questionnaire investigating occupations and hobbies with special emphasis on: Duration of exposure. An exposure index was calculated for each interviewed subject according to the following formula: hours/day × days/year × years. Patients with an exposure index >2400 hours were considered as 'exposed.' The 2400 hour cut-off value was chosen on the basis of previous reports indicating that this figure represents heavy exposure to genotoxic agents. Statistical analysis was obtained using SPSS-10®. Between 1991 and 2001, 61 young males with adenocarcinoma of the prostate were identified, of whom 56 patients with a mean age of 47 years (range: 40–49) had complete records of treatment and could be contacted for completion of the questionnaire. The most common stage at presentation was Stage III and the mean Gleason's score was 7.5 (range 5–9). Interestingly, almost a third (16/56, 28.6%) of patients had stage IV disease at presentation. 37/56 (66.1%) patients had 'significant' exposure in our study. In addition, interestingly, the mean survival in the subgroup of patients with pesticide exposure was 11.3 months (SD: +/- 2.3 months), while the mean survival in the patients without pesticide exposure (n = 19) was 20.1 months (SD: +/- 3.1 months), with p-value <0.01. Although our study is relatively small, it does reveal preliminary evidence linking pesticide exposure to the early development of, possibly aggressive, prostate adenocarcinoma. Future, larger, epidemiological studies are needed to confirm the findings of our study.
BackgroundThe rate of detection of HER-2/neu and CD117 (c-kit) overexpression in small cell lung cancer (SCLC) has varied widely; between 5–35% and 21–70% respectively.MethodsTo evaluate the relationship between pesticide exposure and HER-2/neu and CD117 overexpression in extensive stage SCLC (ESSCLC), we identified patients with ESSCLC and assessed pesticide exposure using a predetermined questionnaire. An exposure index (hours/day × days/year × years) ≥ 2400 hours was considered as 'exposed.' HER-2/neu overexpression was evaluated on archival tissue using the DAKO Hercep test, and CD117 testing was performed using immunohistochemistry (A4052 polyclonal antibody).Results193 ESSCLC patients were identified. Pesticide exposure data could be obtained on 174 patients (84 females and 109 males) with a mean age of 68.5 years. 53/174 (30.4%) revealed HER-2/neu overexpression. 54/174 (31.03%) specimens showed CD117 overexpression by IHC. On multivariate analysis, HER-2/neu overexpression was associated with diminished survival (p < 0.001). In comparison, CD117 expression did not have an adverse prognostic value (p = 0.025). 41/53 (77.4%) patients with HER-2/neu overexpression and 47/121 (38.8%) patients without overexpression had exposure to pesticides (odds ratio: 5.38; p < 0.01). Among the cohort tested for CD117, 29/54 (53.7%) patients with CD117 overexpression and 59/120 (49.2%) patients without CD117 overexpression had pesticide exposure (odds ratio: 1.18; p = 0.12).ConclusionPesticide exposure affects HER-2/neu but not CD117 overexpression. Future studies are needed to determine specific pesticide(s)/pesticide components that are responsible for HER-2/neu overexpression in ESSCLC, and to validate our findings in other solid tumors that overexpress HER-2/neu.
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