Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma

Kibbelaar, Robby E.; Moolenaar, Kitty E.C.; Michalides, Rob; Bodegom, Peter C. Van; Vanderschueren, R. G. J. R. A.; Wagenaar, Sjoerd Sc.; Dingemans, K. P.; Bitter‐Suermann, D.; Dalesio, Otilia; Zandwijk, Nico van; Mooi, Wolter J.

doi:10.1016/0277-5379(91)90379-r

Cited by 83 publications

(38 citation statements)

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“…Although the reason for this inconsistency is unclear, it could be attributable to the difficulty in quantitative measurements by IHC. Indeed, although neuroendocrine markers have been detected in a considerable proportion of NSCLCs by IHC (16)(17)(18)(19)(20)(21)(22)(23)(24)(25), positive (18)(19)(20)(21)(22) and negative findings (23)(24)(25) have been reported in terms of the association between the IHC characteristics and the prognosis. Another explanation is that NSE expression is not identical to NSE secretion into the blood circulation, as NSE expression has also been detected by immunohistochemistry in various normal human tissues other than nervous and neuroendocrine tissues, including type II alveolar epithelial cells (26).…”

Section: Discussionmentioning

confidence: 99%

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Inomata

Hayashi

Yamamoto

et al. 2015

Molecular and Clinical Oncology

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Abstract. Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment. IntroductionEpidermal growth factor receptor (EGFR) gene mutation is an important predictor of the response to EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. Gefitinib treatment yields a longer progression-free survival (PFS) rate than cytotoxic drug therapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations, including exon 19 deletion and exon 21 L858R (1-3). However, an important clinical problem is that in the majority of cases, the tumor cells soon acquire resistance to gefitinib.Several mechanisms of acquired resistance to gefitinib have been proposed. Hepatocyte growth factor has been shown to induce resistance to gefitinib of lung adenocarcinomas harboring EGFR gene mutations (4). An investigation of 37 cases with acquired resistance to gefitinib revealed the presence of the EGFR T790 mutation, MET amplification, transition from NSCLC to small cell lung cancer (SCLC), or PIK3CA mutation in these cases (5).Blood levels of pro-gastrin releasing peptide (pro-GRP) and neuron-specific enolase (NSE) have been reported to be frequently elevated in patients with SCLC (6), and their measurement has been utilized for diagnosis or evaluation of the treatment outcomes in these patients. Furthermore, elevation of the pretreatment plasma NSE level has also been associated with poor outcomes in patients with NSCLC (7-11). We hypothesized that the blood level of pro-GRP and/or NSE may be associated with the clinical course following initiation of gefitinib therapy in patients with NSCLC harboring EGFR gene mutations. To endorse its va...

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Section: Discussionmentioning

confidence: 99%

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Inomata

Hayashi

Yamamoto

et al. 2015

Molecular and Clinical Oncology

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“…Potentially useful prognostic factors however are much more numerous [28]. A partial list of such factors includes conventional biochemical tests [29][30][31], and newer tests based on the experimental evidence arising at the cellular and molecular level [32]. Preliminary reports suggest that additional factors might be important, all gathered under the comprehensive term of "quality of life" [2,4,5].…”

Section: Discussionmentioning

confidence: 99%

Depressive reactions to lung cancer are common and often followed by a poor outcome

Buccheri¹

1998

Eur Respir J

113

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In diverse human malignancies, including lung cancer, quality of life (QOL) affects the clinical outcome of patients. Many QOL dimensions, however, are influenced by physical status. The current study was undertaken to delineate the role of depression, a state of mind not necessarily influenced by somatic factors. All patients, seen for a newly diagnosed carcinoma of the lung, received a copy of the Self-rating Depression Scale (SDS) proposed by W.W.K. Zung. One hundred and thirty three patients were able and willing to complete the questionnaire. A depression index was calculated, as originally described. Nineteen other prognostically important variables were recorded and available for evaluation. Among the 95 patients who completed all 20 items included in the questionnaire, 53 had an SDS index < or = 50 (no depression), while 42 were moderately or severely depressed (SDS index >50). The survival of depressed patients was significantly lower (p=0.048). Diverse SDS subscales were associated with survival, in either univariate or multivariate analysis. SDS item 19, "I feel that others would be better off if I were dead", emerged as the most significant one. A multivariate model of survival, constructed using only SDS data, had a global Chi-squared value of 29.78, and a p-value of 0.00023. Based on this evidence, it appears that a relationship does exist between patients' depression and prognosis, at least in lung cancer. Further studies are needed to clarify the prognostic effect of depression in more specific (and homogeneous) subgroups of patients.

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“…Expression in a series of lung carcinomas was associated with significantly reduced patient survival (Kibbelaar et al, 1991), and the embryonic, less adhesive form of NCAM has been found in Ewing's sarcoma, Wilms' tumor, and neuroblastoma (Edelman and Crossin, 1991).…”

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confidence: 99%

Cell Adhesion Molecules and Oral Cancer

Thomas

Speight

2001

Critical Reviews in Oral Biology & Medicine

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Cell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. As well as having a structural role, CAMs function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation. Cell adhesion molecules are essential for maintaining stable tissue structure. However, cell adhesion must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, cells alter their cell-cell and cell-matrix interactions by virtue of altered expression and function of CAMs. The expression of CAMs is normally tightly regulated, thereby controlling cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that many of the characteristics of tumor cells are attributable to the aberrant expression or function of CAMs.Integrins and E-cadherin are the most important CAMs expressed by stratified squamous epithelium. Altered expression of these molecules has been found in oral carcinoma, where loss of CAM expression is often seen in poorly differentiated lesions.However, up-regulation of certain integrins, such as av16, has consistently been found in oral cancer, suggesting that it may play an active role in disease progression.Key words. Oral cancer, cell adhesion molecules, integrins, cadherins, selectins, immunoglobulin superfamily, CD44. (I) IntroductionCell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. Cell adhesion is critical in the dynamic processes necessary for tissue morphogenesis in development and the maintenance of complex differentiated tissues in adult organisms. CAMs serve in these roles by virtue of their capacity to connect the exterior of the cell with the interior. They form structural linkages between the cell cytoskeleton and the extracellular matrix or between cells, and also function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation ( Fig. 1).Cell adhesion molecules are essential for maintaining the stable structure of stratified squamous epithelium. In normal epithelium, keratinocytes are attached to each other and to the underlying basement membrane. Cell adhesion, however, must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, keratinocytes alter their cell-cell and cell-ECM interactions by virtue of altered expression and function of CAMs.The expression of cell adhesion molecules is normally tightly regulated-forming, persisting, or declining in an ordered fashion. This allows for controlled cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that man...

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Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma

Cited by 83 publications

References 11 publications

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Depressive reactions to lung cancer are common and often followed by a poor outcome

Cell Adhesion Molecules and Oral Cancer

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