[show abstract][hide abstract] ABSTRACT: To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2 (HER2) antibodies in whole-tissue sections and tissue microarrays (TMAs) of a series of gastric tumors.
We present a comparative analysis of three anti-HER2 antibodies (HercepTest, 4B5 and SP3) using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December 2008 at a Brazilian cancer hospital. The data on the patients' age, sex, the anatomical location of the tumor and the Lauren's histological classification were collected from clinical and pathological records. The immunohistochemical (IHC) results were examined by two pathologists and the cases were classified as positive (3+), equivocal (2+) and negative (0 or 1+), according to the criteria of the IHC scoring system of gastric cancer. TMAs and whole-tissue sections were evaluated separately and independently. All cases yielding discordant IHC results and/or scored as 2+ were subjected to dual-color in situ hybridization in order to determine the final HER2 status. Besides determining the sensitivity and predictive value for HER2-positive status, we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic (ROC) curve. The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.
Intratumoral heterogeneity of HER2 expression was observed with all antibodies. HER2-positive expression (3+) in the whole-tissue sections was observed in 23 cases (11.6%) using the 4B5 antibody, in 18 cases (9.1%) using the SP3 antibody and in 10 cases (5.1%) using the HercepTest antibody. In the TMAs, 11 positive cases (5.6%) were identified using SP3 antibody, 9 (4.6%) using the 4B5 antibody and 6 (3%) using the HercepTest antibody. The sensitivity using whole-tissue sections and TMA, respectively, was 95.2% and 42.9% with 4B5, 90.5% and 66.7% with SP3 and 47.6% and 42.9% with HercepTest. The accuracy, calculated from the area under the ROC curve, using whole-tissue sections and TMA, respectively, was 0.91 and 0.79 by 4B5, 0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest. The concordance of the results obtained using whole-tissue sections and TMA was 97.4% (Kappa 0.75) using HercepTest, 85.6% (Kappa 0.56) using SP3 and 84.1% (Kappa 0.38) using 4B5.
The use of the 4B5 antibody on whole-tissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.
World Journal of Gastroenterology 10/2013; 19(38):6438-46. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. METHODS: This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. RESULTS: Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. CONCLUSIONS: According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Adjuvant chemoradiotherapy (CRT) is the standard treatment in Western countries for gastric cancer patients submitted to curative resection. However, the role of adjuvant CRT in gastric cancer treated with D2 lymphadenectomy has not been well defined. METHODS: We conducted a retrospective study in patients with stage II to IV gastric adenocarcinoma with no distant metastases, who underwent curative resection with D2 lymphadenectomy between January 2002 and December 2007. The present study compared the 3-year overall survival of two treatments (adjuvant CRT according to the INT 0116 trial versus resection alone). Survival curves were estimated by the Kaplan-Meier method and compared with a log-rank test. Multivariate analysis of prognostic factors was performed by the Cox proportional hazards model. RESULTS: A total of 185 patients were included, 104 patients (56 %) received adjuvant CRT and 81 received resection alone. The 3-year overall survival was 64.4 % in the CRT group and 61.7 % in the resection-alone group (p: 0.415). However, according to the Cox proportional hazards model, adjuvant CRT was a prognostic factor for 3-year overall survival (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.26-0.82, p: 0.008). CONCLUSIONS: In the present study, adjuvant CRT was associated with a lower risk of death over a 3-year period in gastric cancer patients treated with D2 lymphadenectomy.
[show abstract][hide abstract] ABSTRACT: Three hundred and sixty patients with gastric carcinoma were evaluated by laparoscopy. The following tumor attributes were used in the staging workup: serosal infiltration, tumor fixation, metastasis to lymph nodes, peritoneal dissemination, and liver metastasis. For the detection of liver metastases, subgroups of these patients were also tested by liver scintigraphy, ultrasonography, and serum alkaline phosphatase determination. Use of diagnostic indexes with their confidence intervals provided an objective means of assessing performance for the various combinations of tests and attributes. The attributes which were most accurately detected by laparoscopy were peritoneal dissemination and liver metastases with 89.4% and 96.5% efficiency, respectively. Laparoscopy was a superior diagnostic method when compared to the other tests for detection of liver involvement. Scintigraphy and ultrasonography presented comparable sensitivities, 78.7% and 78.6%, respectively (as opposed to 87.2% of laparoscopy), but the former yielded a high rate of false-positive results, 62.6%. Detection of liver metastases by assaying alkaline phosphatase levels was the least sensitive diagnostic alternative examined.
[show abstract][hide abstract] ABSTRACT: The accuracy of an alternative method of preparing cytologic smears from material collected under laparoscopic examination was studied. "Washed-biopsy" cytology was performed by saline solution lavage of the fragments using a cytocentrifuge. Rich and well-preserved cellularity was obtained. Among 51 cases, cytology revealed 12 benign, 3 suspicious and 36 malignant cases, including 9 true negatives, 3 false negatives and 36 true positives. Suspicious cases were excluded from the analysis. The sensitivity, specificity, positive and negative predictive values, and efficiency, when comparing the cytologic to the definitive diagnoses, were, respectively, 92.3%, 100.0%, 100.0%, 75.0% and 93.7%. We recommend the routine use of the washed-biopsy method in laparoscopic examinations to improve the accuracy of cytologic investigations.