HER-2/neu and CD117 (c-kit) overexpression in patients with pesticide exposure and extensive stage small cell lung carcinoma (ESSCLC).

BACKGROUND: The 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. METHODS: To 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 x days/year x years) > or = 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). RESULTS: 193 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). CONCLUSION: Pesticide 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.

Effect of pesticide exposure on HER-2/neu overexpression seen in patients with extensive stage small cell lung carcinoma.

PURPOSE: The aim of this study was to evaluate the relationship, if any, between pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive stage small cell lung cancer (ESSCLC). EXPERIMENTAL DESIGN: The records of all patients with a diagnosis of ESSCLC from January 1991 through April 2001 were reviewed in our retrospective study. Pesticide risk (herbicide and insecticide) was assessed by telephone interviews using a predetermined questionnaire with emphasis on type of exposure, use of protective measures, and duration of exposure. An exposure index was calculated (h/day x days/year x years), and patients with an index > 2400 h were considered as exposed. HER-2/neu overexpression was assessed by immunohistochemistry using the Hercep test developed by Dako. Statistical analysis was performed using SPSS-10. RESULTS: A total of 193 patients (84 females and 109 males), with a mean age of 68.5 years (range, 42-90 years) were included in the study. Of these, 57 (29.5%) revealed HER-2/neu overexpression by immunohistochemistry. After adjusting for age, smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu overexpression was associated with a statistically significant diminished survival (P < 0.001; Mann-Whitney U test). We contacted 53 of 57 patients with overexpression and 121 of 136 patients without HER-2/neu overexpression to ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with HER-2/neu overexpression and 47 of the 121 patients without overexpression (38.8%) were exposed to pesticides. We found that patients with history of pesticide exposure had a higher risk of having HER-2/neu overexpression (odds ratio, 5.38; P < 0.01, 95% confidence interval, 2.5-11.2) CONCLUSIONS: HER-2/neu is overexpressed in approximately 30% patients with ESSCLC and is associated with decreased survival. Also, pesticide exposure seems to be related to HER-2/neu overexpression seen in our patient population. Future studies are needed to validate our findings and also to determine which pesticide(s)/pesticide components are actually responsible for HER-2/neu overexpression seen in ESSCLC.

Immunohistochemical determination of HER-2/neu, c-Kit (CD117), and vascular endothelial growth factor (VEGF) overexpression in malignant melanoma.

PURPOSE: To determine the prevalence and evaluate the possible prognostic value of the molecular targets in malignant melanoma, we studied the overexpression of HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be overexpressed in the superficial spreading type and VEGF was overexpressed preferentially in the amelanotic melanoma type. CONCLUSIONS: 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.

Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma.

PURPOSE: To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). PATIENTS AND METHODS: VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative. RESULTS: Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1-93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup( P=0.01, by log-rank sum test). CONCLUSION: Twenty-four point nine percent of STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.

HER-2/neu and CD117 (C-kit) overexpression in hepatocellular and pancreatic carcinoma.

BACKGROUND: Hepatocellular carcinoma has an overall 5-year survival of less than 5%. Similarly, pancreatic cancer has a mortality: incidence ratio of 0.99. The aim of this study was to determine the prevalence of HER-2/neu and c-kit (CD117) overexpression and to identify a possible predictive role in patients with these two malignancies. MATERIALS AND METHODS: We performed a retrospective study on archival specimens of subjects with hepatocellular and pancreatic carcinoma. HER-2/neu and CD117 overexpression were evaluated by immunohistochemistry. RESULTS: Thirty-three patients with pancreatic carcinoma and 25 patients with hepatocellular carcinoma were identified. The mean age was 71.7 years for patients with pancreatic carcinoma and 66 years for patients with hepatocellular carcinoma. Two patients with hepatocellular carcinoma and none with pancreatic cancer overexpressed HER-2/neu, while 2 patients with pancreatic carcinoma and 1 patient with hepatocellular carcinoma overexpressed CD117. CONCLUSION: HER-2/neu and CD117 are not significantly overexpressed in either cancer. There appears to be no role for the use of trastuzumab in either malignancy. Similarly, while there appears to be no role for tyrosine kinase inhibitors in the treatment of hepatocellular carcinoma, further larger studies are necessary in pancreatic adenocarcinoma.

Immunohistochemical detection of HER-2/neu, c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas.

PURPOSE: The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS. MATERIALS AND METHODS: We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system. RESULTS: Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03). CONCLUSION: VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.

Ineffectiveness of measuring routine vital signs in adult inpatients with deep venous thrombosis.

The purpose of this study was to evaluate the benefit, if any, of routine monitoring of vital signs on clinical outcomes in hospitalized patients with deep venous thrombosis (DVT). One hundred forty-nine patients with DVT included in this study were categorized into two groups: those that underwent measurement of vital signs every 6 hours or those that had vital signs measured every 8 hours. Vital signs included pulse, blood pressure, respiratory rate, and temperature. Frequency of measurement of vital signs did not alter average length of star, for patients with every-4-hours measurement, this was 5.16 days and was not statistically significant from patients with every-8-hours measurement, who stayed an average of 4.85 days (p = 0.507). Similarly, more frequent vital sign evaluation did not result in a statistically significant difference in survival, progression of disease, nor did it predict the disposition of the patient. These results suggest that present frequency of measurement of vital signs is not cost or time effective because they do not result in a favorable outcome, length of stay, or disposition. The study further serves to highlight the need for an individualized assessment of vital sign measurement, because this will also lead to a more efficient allocation of hospital resources.

Ineffectiveness of the measurement of 'routine' vital signs for adult inpatients with community-acquired pneumonia.

More frequent vital sign evaluation does not result in a statistically significant difference in survival or the number of transfers to the intensive care unit (for progression of disease) after adjusting for age, gender, duration of intravenous antibiotics and comorbid conditions.

Role of her-2/neu overexpression and clinical features at presentation as predictive factors in meningiomas.

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.