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      High expression of cyclooxygenase 2 is an indicator of prognosis for patients with esophageal squamous cell carcinoma after Ivor Lewis esophagectomy

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          Abstract

          Background

          The poor prognosis of esophageal squamous cell carcinoma ( ESCC) is attributed to a high recurrence rate after surgery. Cyclooxygenase 2 ( COX2) is an important regulator of cell growth, differentiation, apoptosis, and transformation. COX2 overexpression is significantly associated with the tumorigenesis and progression of diverse cancers; however, its expression and significance in ESCC remains unclear.

          Methods

          We enrolled 118 patients with ESCC who had undergone Ivor‐Lewis esophagectomy. The expression profile of COX2 was examined by immunohistochemistry.

          Results

          A high expression of COX2 correlated with a higher T staging ( P = 0.014), lower differentiation degree ( P = 0.002), lymph node metastasis ( P = 0.009), recurrence status ( P = 0.004), and tumor node metastasis ( TNM) stage ( P = 0.001). Cox regression analysis showed that TNM stage ( P = 0.001), differentiation degree ( P = 0.001), and high COX2 expression ( P = 0.004) were independent risk factors of prognosis.

          Conclusion

          Our data indicated that COX2 expression level is associated with key clinicopathological features and could be an effective biomarker to predict ESCC prognosis.

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          Expression of cyclooxygenase-2 in human lung carcinoma.

          H. Wolff, K Saukkonen, S Anttila … (1998)
          Epidemiological studies indicate that the use of aspirin decreases incidence of and mortality from gastrointestinal cancers. A major target of aspirin and other nonsteroid anti-inflammatory drugs is cyclooxygenase (Cox), the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned (Cox-1 and Cox-2), of which Cox-2 has recently been found to be expressed in several human carcinomas. We have now studied the expression of Cox-2 mRNA and protein in human lung adenocarcinoma, squamous cell carcinoma, and small cell lung cancer. Cox-2 mRNA steady-state levels were high in well-differentiated adenocarcinoma samples, but low in poorly differentiated adenocarcinoma, squamous cell carcinoma, and small cell lung cancer, as detected by Northern blot analysis. Immunohistochemistry showed Cox-2 staining in 19 of 21 adenocarcinomas. However, well-differentiated adenocarcinomas contained more Cox-2 staining than the poorly differentiated ones. Expression of the Cox-2 protein was also seen in all 11 squamous cell carcinomas studied, although the level of staining seemed to be less than that in the adenocarcinomas. Small cell lung cancer specimens (n = 4) stained with a relatively weak intensity. Interestingly, atypical alveolar epithelium, which associates with asbestosis and idiopathic fibrosing alveolitis and is considered to be a precursor lesion for lung cancer, expressed the Cox-2 protein. Our data, thus, suggest that Cox-2 is expressed in human lung carcinomas and in precursor lesions leading to this malignancy.
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            Non-small cell lung cancer exhibits transcript overexpression of genes associated with homologous recombination and DNA replication pathways.

            Marco Lo Iacono, Raffaele A Calogero, Mauro Papotti … (2009)
            Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-naïve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67%) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were significantly underexpressed. For 7 of 30 (23%) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCC5, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.
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              The recurrence pattern of esophageal carcinoma after transhiatal resection.

              H. Obertop, J Tijssen, Marlies Hulscher … (2000)
              There is much controversy about the optimal resection for carcinoma of the esophagus. Little is known about the pattern of recurrence after transhiatal resection for esophageal carcinoma. We retrospectively reviewed the charts of 149 patients who underwent transhiatal esophagectomy for carcinoma of the mid or distal esophagus or gastroesophageal junction between June 1993 and June 1997. Recurrence was classified as locoregional or distant recurrence. Nine patients with macroscopically evident tumor left after resection and three patients (2.0%) who died in the hospital were excluded from the analysis. This left 137 patients; 105 men and 32 women with a median age 65 years (range 37 to 84 years). There were 95 adenocarcinomas (69.3%) and 42 squamous cell carcinomas (30.7%). Overall the median followup was 24.0 months (range 1.4 to 69.2 months). For patients alive at the end offollowup without recurrence, the median followup was 36.5 months (range 23.6 to 69.2 months). Seven patients died of other causes. The median interval between operation and recurrence was 11 months (range 1.4 to 62.5 months) for patients who had recurrence, with no significant difference in interval between locoregional and systemic recurrence. Seventy-two of the 137 patients (52.6%) developed recurrent disease. Thirty-two patients (23.4%) developed locoregional recurrence only, 21 patients (15.3%) developed systemic recurrence only, and 19 patients (13.9%) had a combination of both. In only 8.0% of all patients was there recurrence in the cervical lymph nodes. The most frequent sites of distant recurrence were liver (37.5%), bone (25.0%), and lung (17.5%). Recurrence was related to postoperative lymph node status (p<0.001) and the radicality of the operation (p<0.001) in multivariate analysis. Recurrence was not associated with localization or histologic type of the tumor. Recurrence after transhiatal resection is an early event. Almost 40% of patients developed locoregional recurrent disease. For this patient group a more extended procedure may be of benefit, especially in the patients (23.4%) with locoregional recurrence in whom this is the only site of recurrent disease. But the potential benefit of a more extended procedure has to be balanced against a possible increase in perioperative morbidity and mortality.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Thorac Cancer
                Journal ID (iso-abbrev): Thorac Cancer
                Journal ID (doi): 10.1111/(ISSN)1759-7714
                Journal ID (publisher-id): TCA
                Title: Thoracic Cancer
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1759-7706
                ISSN (Electronic): 1759-7714
                Publication date (Electronic): 04 January 2016
                Publication date (Print): 26 April 2016
                Volume: 7
                Issue: 3 ( doiID: 10.1111/tca.2016.7.issue-3 )
                Pages: 310-315
                Affiliations
                [ 1 ] Department of Thoracic SurgeryProvincial Hospital Affiliated to Shandong University Jinan ShandongChina
                [ 2 ] Department of GastroenterologyProvincial Hospital Affiliated to Shandong University Jinan ShandongChina
                Author notes
                [*] [* ] Correspondence

                Zhou Wang, Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Ji'nan 250021, Shandong Province, China.

                Tel: +86 531 68777884

                Fax: +86 531 87902348

                Email: 43572850@ 123456qq.com

                Article
                Publisher ID: TCA12329
                DOI: 10.1111/1759-7714.12329
                PMC ID: 4846619
                PubMed ID: 27148416
                SO-VID: 3e9014d2-2672-49e6-8f8b-e1f9d1f9ce3f
                Copyright © © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 24 August 2015
                Date accepted : 23 November 2015
                Page count
                Pages: 6
                Categories
                Subject: Original Articles
                Subject: Original Article
                Custom metadata
                source-schema-version-number 2.0
                component-id tca12329
                cover-date May 2016
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.8 mode:remove_FC converted:26.04.2016

                Keywords: cox2,esophageal squamous cell carcinoma,ku80,prognosis,recurrence
                Data availability:
                Keywords: cox2, esophageal squamous cell carcinoma, ku80, prognosis, recurrence

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