Activation state egfr and STAT-3 as prognostic markers in resected non-small cell lung cancer

Cortas, Tania; Eisenberg, Rosana; Fu, Pingfu; Kern, Jeffrey A.; Patrick, Lauren; Dowlati, Afshin

doi:10.1016/j.lungcan.2006.11.003

Cited by 48 publications

(37 citation statements)

References 25 publications

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“…ERK translocates to the nucleus and phosphorylates transcription factors that regulate genes controlling cell proliferation, including cyclin D1 (Cesana et al, 2006) that is overexpressed in 30 -50% of colorectal carcinomas and is associated with a poor prognosis (Arber et al, 1996;McKay et al, 2000). Phospho-EGFR was not prognostic in our study which is concordant with the data obtained from non-small cell lung cancer and breast cancer patients, wherein no associations with survival were found (Cortas et al, 2007;Nieto et al, 2007). Although we studied a major EGFR phosphorylation site, it is possible that activation at other EGFR autophosphorylation sites may confer prognostic information.…”

Section: Discussionsupporting

confidence: 89%

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Rego

Foster²,

Smyrk

et al. 2009

Br J Cancer

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BACKGROUND: Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined. METHODS: Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n ¼ 388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival. RESULTS: Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P ¼ 0.03). Tumours overexpressing EGFR (P ¼ 0.0002) or phospho-EGFR (P ¼ 0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P ¼ 0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P ¼ 0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P ¼ 0.042) after adjustment for stage, histological grade, age, and MMR status. CONCLUSION: Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.

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Section: Discussionsupporting

confidence: 89%

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Rego

Foster²,

Smyrk

et al. 2009

Br J Cancer

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“…Its expression was observed more frequently in smaller tumors, 27 and no relationship with overall survival was found. 26,28 However, the results of a recent meta -analysis have suggested that high STAT3 mRNA and protein levels have poor prognostic significance in NSCLC, associated with poorly differentiated carcinoma, stage III-IV cancer, and lymph node metastasis. 29 In our study, the highest frequency of the increased pSTAT3 expression was found in pT3+pT4 tumor samples (95% of NSCLC samples) and in samples with lymph node metastasis (42% in the N1 group and 56% in the N2 group, according to the pTNM classification).…”

Section: 16mentioning

confidence: 99%

Immunoexpression analysis of selected JAK/STAT pathway molecules in non-small cell lung cancer patients

Pastuszak-Lewandoska¹,

Domańska-Senderowska²,

Kordiak³

et al. 2017

Polish Archives of Internal Medicine

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“…8102, Cell Signalling) was used to validate the antibody for p-EGFR. pY1173-EGFR immunostaining was mainly membranous and was graded as 0 (o5% positive cells), 1 þ (5 -19% positive cells), 2 þ (20 -50% positive cells) and 3 þ (450% positive cells) (Cortas et al, 2007).…”

Section: Immunohistochemistry For Egfrmentioning

confidence: 99%

Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC

et al. 2008

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In non-small-cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) and K-RAS mutations of the primary tumour are associated with responsiveness and resistance to tyrosine kinase inhibitors (TKIs), respectively. However, the EGFR and K-RAS mutation status in metastases is not well studied. We compared the mutation status of these genes between the primary tumours and the corresponding metastases of 25 patients. Epidermal growth factor receptor and K-RAS mutation status was different between primary tumours and corresponding metastases in 7 (28%) and 6 (24%) of the 25 patients, respectively. Among the 25 primary tumours, three 'hotspot' and two non-classical EGFR mutations were found; none of the corresponding metastases had the same mutation pattern. Among the five (20%) K-RAS mutations detected in the primary tumours, two were maintained in the corresponding metastasis. Epidermal growth factor receptor and K-RAS mutations were detected in the metastatic tumours of three (12%) and five (20%) patients, respectively. The expressions of EGFR and phosphorylated EGFR showed 10 and 50% discordance, in that order. We conclude that there is substantial discordance in EGFR and K-RAS mutational status between the primary tumours and corresponding metastases in patients with NSCLC and this might have therapeutic implications when treatment with TKIs is considered.

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Activation state egfr and STAT-3 as prognostic markers in resected non-small cell lung cancer

Cited by 48 publications

References 25 publications

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status

Immunoexpression analysis of selected JAK/STAT pathway molecules in non-small cell lung cancer patients

Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC

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