Tissue microarray analysis of EGFR and HER2 oncogene copy number alterations in squamous cell carcinoma of the larynx

Koynova, Denitsa; Tsenova, V.; Jankova, Renata; Gurov, Plamen Borisov; Toncheva, Draga

doi:10.1007/s00432-004-0627-y

Cited by 31 publications

(19 citation statements)

References 28 publications

(28 reference statements)

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“…As IHC stainings are more routinely performed than FISH analysis in many institutes, the antibody and the protocol that we used could very well be used as a pseudomarker for amplification. The frequency that we found is in good agreement with the previously described amplification frequency of EGFR in HNSCC (Freier et al, 2003;Koynova et al, 2005;Temam et al, 2007).…”

Section: Discussionsupporting

confidence: 81%

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

et al. 2010

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BACKGROUND: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is B50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. METHODS: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. RESULTS: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1 -4.6; P ¼ 0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2 -27.4; P ¼ 0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2 -6.5; P ¼ 0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance. CONCLUSION: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC.

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Section: Discussionsupporting

confidence: 81%

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

et al. 2010

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“…Some studies have focused on validation of immunohistochemical analysis of EGFR expression on TMAs, while only limited reports have validated FISH analysis or recently developed mutant EGFR-specific antibodies for IHC using TMAs in several types of cancer [35,36,39]. We are aware of the limited interest in TMA technology as a daily routine test.…”

Section: Discussionmentioning

confidence: 97%

“…Fluorescence in situ hybridization (FISH) was performed on paraffin-embedded TMAs and whole-tissue 4-μm sections according to a protocol described previously [36]. At least 100 non-overlapping interphase nuclei per core were analyzed blindly and independently by two pathologists (MI and VH).…”

Section: Fluorescence In Situ Hybridizationmentioning

confidence: 99%

Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma

et al. 2010

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Specific inhibitors targeting the epidermal growth factor receptor (EGFR) can increase survival rates in certain lung adenocarcinoma patients with mutations in the EGFR gene. Although such EGFR-targeted therapies have been approved for use, there is no general consensus among surgical pathologists on how the EGFR status should be tested in lung adenocarcinoma tissues and whether the results of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mutational analysis by molecular methods correlate. We evaluated the EGFR status in 61 lung adenocarcinomas by IHC (using total and mutant-specific antibodies against EGFR), by FISH analysis on tissue microarrays (TMAs), and by direct sequencing. The results of each method were compared using χ² and κappa statistics. The sensitivity and negative predictive value estimating the presence of abnormal EGFR for each test was calculated. The results show that, with respect to expression patterns and clinicopathological parameters, the total and mutant-specific EGFR detected by immunohistochemistry and FISH analysis on TMAs are valid and are equivalent to conventional methods performed on whole-tissue sections. Abnormal EGFR was detected in 52.4% of patients by IHC, FISH, and sequencing. The best sensitivity (100%) and negative predictive value (100%) was determined by evaluating the EGFR status with all methods. Testing for molecular changes in EGFR using a single test is likely to underestimate the presence of EGFR abnormalities. Taken together, these results demonstrate the high potential of TMAs to test for the major mechanisms of EGFR activation in patients with lung adenocarcinoma.

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“…These data fit well with observations in other squamous carcinoma types. HER-2 amplification is less frequent in squamous cell carcinoma of the lung than in adenocarcinoma of the lung [55][56][57][58] and rather infrequent in most prevalent squamous cell carcinomas like head and neck, 59,60 skin 61 or cervical carcinomas. 62,63 The current use of molecular diagnostics for targeted cancer therapy is depending on the assumption that all metastases will show the same target gene alteration as observed in the primary tumor.…”

Section: Discussionmentioning

confidence: 97%

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

et al. 2007

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HER-2 is the target for antibody based treatment of breast cancer (Herceptin s ). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTestt; DAKO) and fluorescence in situ hybridization (FISH; PathVysiont; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (Po0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high-level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptin s should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin s .

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Tissue microarray analysis of EGFR and HER2 oncogene copy number alterations in squamous cell carcinoma of the larynx

Abstract: These results suggest that EGFR amplification is a relatively rare event in larynx carcinogenesis that obviously does not predispose to tumor progression.

Cited by 31 publications

References 28 publications

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

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