Marker For Pulmonary Adenocarcinomas Research Articles

High Expression of NT5DC2 Is a Negative Prognostic Marker in Pulmonary Adenocarcinoma.

Simple SummaryLung cancer is the leading cause of cancer related deaths and non-small cell lung cancer (NSCLC) is its most relevant subtype. Here, we present data on p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein- and gene-expression and its clinical implication and prognostic value. NT5DC2 overexpression was associated with advanced lymphonodal spread and reduced survival in patients with adenocarcinoma of the lung. Moreover, dysregulated p53 in combination with overexpressed NT5DC2 might promote malignancy by interaction with cancer associated fibroblasts.Via immunohistochemistry (IHC) on tissue micro arrays (TMA) clinical and prognostic impact of p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein expression was evaluated in 252 NSCLC patients. Confirmatory, gene expression database. mRNA levels of NT5DC2 were studied in 1925 NSCLC patients. High protein expression of NT5DC2 resulted in reduced median overall survival (OS) of patients with stage I-III adenocarcinoma (ADC) (Log Rank p = 0.026, HR 2.04 (1.08–3.87)), but not in squamous cell carcinoma (SCC) (p = 0.514, HR 0.87 (0.57–1.33)). Findings on OS were reproduced via gene expression analysis in ADC (p < 0.001, HR 1.64 (1.30–2.08)) and SCC (p = 0.217, HR 0.86 (0.68–1.09)). Yet, NT5DC2 mRNA levels were higher in SCC compared to ADC (p < 0.001) and in pN2 tumors compared to pN0/1 tumors (p = 0.001). Likewise, NT5DC2 protein expression associated with high-grade SCC. Moreover, NT5DC2 expression was positively correlated with p53 protein (p = 0.018) and TP53 gene expression (p < 0.001) and its survival effect was p53 dependent. While p53 expression was negatively associated with the presence of CD34+ cancer associated fibroblasts (CAFs), NT5DC2 expression insignificantly tended to higher levels of SMA+ CAFs (p = 0.065).

Cytomorphological Features of Lung Adenocarcinoma with Anaplastic Lymphoma Kinase Gene Rearrangement.

Background:The anaplastic lymphoma kinase (ALK) gene rearrangement is a predictive and prognostic marker in pulmonary adenocarcinoma. A series of clinical and pathological features have been documented in patients who harbor this translocation.Aims:The objectives of this study were to analyze the specific cytomorphological features of lung adenocarcinoma that harbored the ALK gene rearrangement and to compare the morphological features with the mutation-negative cases.Materials and Methods:The study sample of 40 cases included 15 ALK-positive cases and 25 ALK-negative cases. After the diagnosis was established, testing for ALK rearrangement was on the histopathology sample. The corresponding fine-needle aspiration cytology slides were retrieved from the records and cytomorphological features were analyzed.Results:A comparison of pattern between the ALK-positive and ALK-negative group revealed that the sheet-like pattern and singly scattered cells were more common in the ALK-positive group. Moderate-to-severe nuclear pleomorphism was identified in 80% of ALK-positive cases and 72% of ALK-negative cases. The presence of mucinous features and/or signet ring morphology was the most striking feature of ALK-positive cases with P value of 0.002. The presence of necrosis in the background was identified in 80% of ALK-positive cases and was statistically significant (P = 0.001).Conclusion:This is among the few studies from India, where a detailed analysis of the cytomorphological features of cases with ALK phenotype versus the mutation negative cases has been performed.

Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression

The human epididymis 4 (HE4) protein is expressed in the epididymis and respiratory tract. We previously reported that HE4 is also expressed in pulmonary adenocarcinoma. The purpose of this study was to investigate serum levels of HE4 as a biological marker in pulmonary adenocarcinoma. As the trained set, 102 patients with pulmonary adenocarcinoma who underwent surgery in our institute from 2008 to 2011 were evaluated. They were compared with 58 healthy controls and 16 cases of benign lung disease. In the validation, we used 104 patients with pulmonary adenocarcinoma operated on between 2000 and 2007. Postoperative changes of serum HE4 levels were investigated in 35 patients. The level of HE4 was determined by enzyme immunometric assay and compared with clinicopathological factors. In the trained set, HE4 levels in sera in pulmonary adenocarcinoma were significantly higher than in healthy controls and benign lung disease. Receiver operating characteristic curve showed that HE4 was a good discriminator of pulmonary adenocarcinoma (cut-off point, 50.3 pM; area under curve, 0.825; 95 % confidence interval, 0.76-0.89, p < 0.001). In the validation set, serum HE4 levels were significantly correlated with age, nodal status, and carcinoembryonic antigen. Furthermore, postoperative increase of HE4 serum levels showed a significant correlation with recurrence (p = 0.032). The 5-year overall survival rate was 52.6 % in the HE4-positive group compared with 97.1 % in the HE4-negative group (p = 0.001). These data showed that HE4 expression in sera is associated with progression of pulmonary adenocarcinoma and a possible biomarker.

Expression of dual-specificity tyrosine-(Y)-phosphorylation–regulated kinase 2 (DYRK2) can be a favorable prognostic marker in pulmonary adenocarcinoma

We investigated the possibility of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase gene, to predict survival for patients with pulmonary adenocarcinoma. One hundred forty-four patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis and real-time reverse-transcriptase polymerase chain reaction to determine the expression of DYRK2 and compared this with the clinicopathologic factors and survival. We found no correlation between DYRK2 expression by immunohistochemical and clinicopathologic factors; however, a negative nodal status and negative lymphatic invasion were significantly associated with DYRK2 expression by reverse-transcriptase polymerase chain reaction. Five-year disease-free survival in the DYRK2-positive group (75.4%) was significantly different from that in the negative group (55.4%; P = .03) by immunohistochemical analysis. The 5-year overall survival of 89.2% in the DYRK2-positive group was better than the 66.3% survival of the DYRK2-negative group (P = .01). Quantitative real-time reverse-transcriptase polymerase chain reaction analyses showed a significant difference between positive and negative expressions for disease-free survival (P = .003) and overall survival (P = .007). In multivariate Cox regression analysis, negative DYRK2 protein and messenger RNA expression showed a worse prognostic value of survival (hazard ratio [HR] = 4.7, 95% confidence intervals [CI] = 1.5-14.5, P=.007; HR = 2.5, 95% CI = 1.1-6.1, P = .04, respectively). When we analyzed adenocarcinoma cases except for bronchioloalveolar carcinoma, we found a close correlation between DYRK2 expression by immunohistochemical analysis and nodal status (P = .03). Furthermore, disease-free survivals between positive and negative groups of DYRK2 expression by immunohistochemistry (P = .03) and reverse-transcriptase polymerase chain reaction (P = .02) without bronchioloalveolar carcinoma were significantly different. Overall survivals in both groups showed significant differences by immunohistochemistry (P = .02) but not by reverse-transcriptase polymerase chain reaction (P = .08). These data showed that DYRK2 expression is associated with a favorable prognosis.

Expression and prognostic value of the standard CD44 protein in pulmonary adenocarcinoma.

We examined immunohistochemically the expression of the standard form of CD44 (CD44S) tissue specimens from 164 patients with pulmonary adenocarcinoma. Of the 164 specimens, 79 (48%) expressed CD44S and the incidence of expression correlated with the tumor size. The prognosis for CD44S positive patients was poorer than that of CD44S negative patients. Our findings suggest that CD44S plays an important role in tumor progression and that CD44S expression is a useful prognostic marker for pulmonary adenocarcinomas.

Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma

BACKGROUND Angiogenesis in individuals with various solid tumors has provided useful information on tumor progression and prognosis, and many examples of mast cell (MC) accumulation coupled with angiogenesis can be found in the literature. METHODS Utilizing monoclonal antibodies for tryptase that are specific markers for MC and for the endothelial surface marker CD34, the authors quantified MC infiltration in 180 patients with pulmonary adenocarcinoma who underwent curative tumor resection, to investigate the relation between mast cell density (MCD) and microvessel density (MVD), clinicopathologic factors, and prognosis. RESULTS A significant association was found between MCD and MVD (P < 0.0001). The MC count was significantly related to tumor progression, involving N classification and stage (P = 0.0002 for N classification and P = 0.0015 for stage). A significant difference in the rate of patient survival was detected between patients whose tumors had an MCD defined as high and those whose tumors had an MCD defined as low (P < 0.0001). Multivariate analysis also showed that MCD was significantly related to survival (P = 0.0378). CONCLUSIONS These data indicate that MC infiltration may contribute to tumor angiogenesis and tumor progression, and that MCD is a useful prognostic marker in pulmonary adenocarcinoma. Cancer 2000;88:2686–92. © 2000 American Cancer Society.

Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma

Angiogenesis in individuals with various solid tumors has provided useful information on tumor progression and prognosis, and many examples of mast cell (MC) accumulation coupled with angiogenesis can be found in the literature. Utilizing monoclonal antibodies for tryptase that are specific markers for MC and for the endothelial surface marker CD34, the authors quantified MC infiltration in 180 patients with pulmonary adenocarcinoma who underwent curative tumor resection, to investigate the relation between mast cell density (MCD) and microvessel density (MVD), clinicopathologic factors, and prognosis. A significant association was found between MCD and MVD (P < 0.0001). The MC count was significantly related to tumor progression, involving N classification and stage (P = 0.0002 for N classification and P = 0. 0015 for stage). A significant difference in the rate of patient survival was detected between patients whose tumors had an MCD defined as high and those whose tumors had an MCD defined as low (P < 0.0001). Multivariate analysis also showed that MCD was significantly related to survival (P = 0.0378). These data indicate that MC infiltration may contribute to tumor angiogenesis and tumor progression, and that MCD is a useful prognostic marker in pulmonary adenocarcinoma.

Tumor-Associated Macrophage Infiltration in Pulmonary Adenocarcinoma: Association with Angiogenesis and Poor Prognosis

The relation between tumor-associated macrophage (TAM) density and the density of microvessels was investigated in specimens from 113 patients with pulmonary adenocarcinoma, as was the influence of TAM density on prognosis. The rank correlation test revealed a significant relation between TAM density and microvessel density (y = 14.418 + 0.863x, r = 0.454, p > 0.0001). A significant difference in patient survival rate was detected between tumors with a TAM density defined as high and those with a TAM density defined as low (p < 0.01). Multivariate analysis also showed that TAM density was significantly related to survival (p < 0.05). These data indicate that TAM infiltration may contribute to tumor angiogenesis, and that TAM density is a useful prognostic marker in pulmonary adenocarcinoma.

Autocrine motility factor receptor expression as a prognostic factor in pulmonary adenocarcinoma

Autocrine motility factor receptor (AMF-R) expression was studied immunologically in tissue specimens from 121 patients with pulmonary adenocarcinoma. AMF-R expression was correlated with lymph node metastasis and stage. The prognosis of AMF-R positive patients was poorer than that of AMF-R negative patients. Multivariate analysis showed that AMF-R expression had a significant influence on prognosis. Our findings suggest that AMF-R plays an important role in tumor progression and that AMF-R expression is a useful prognostic marker for pulmonary adenocarcinomas.

Insulin-like growth factor (IGF)-I and IGF-II protein expression in pulmonary adenocarcinoma

Insulin-like growth factor (IGF)-I and IGF-II expression was studied immunologically in tissue specimens from 120 patients with pulmonary adenocarcinoma and was correlated with patient prognosis. Multivariate analysis showed that IGF-II expression had a significant influence on prognosis. Our findings suggest that IGF-I and IGF-II play an important role in tumor progression and that IGF-II is a useful prognostic marker for pulmonary adenocarcinomas.

Prognostic impact of histologic demonstration of Chromogranin A and Neuron Specific Enolase in pulmonary adenocarcinoma

One hundred-fourteen patients with inoperable adenocarcinoma of the lung (ACL) were evaluated by immunohistochemistry with monoclonal antibodies against Neuron Specific Enolase (NSE) and Chromogranin A (Chr A) in order to determine the frequency and prognostic impact of such antigen expression. All patients were previously untreated and received chemotherapy according to a prospective randomized trial. The tumors of 18 patients (16%) had more than 10% positive cells stained with anti-NSE, 59 (52%) had 1-10% positive cells and those of 37 patients (32%) contained no NSE-positive cells. The corresponding figures for Chr A were: 22 patients (19%), 51 patients (45%) and 41 patients (36%), respectively. Forty-four per cent of the patients with more than 10% positive NSE cells responded to chemotherapy (either complete or partial remissions) compared to 17% of the patients with fewer than 10% positive cells (p less than 0.025). The corresponding values for Chr A were 30% responders versus 19% responders (not statistically significant). The median survival for patients with more than 10%, 1-10% or no NSE-positive cells was 262 days, 231 days and 159 days, while, for Chr A it was 245 days, 200 days and 238 days, respectively. The survival curves for both NSE and Chr A according to the various levels of positivity were not significantly different. The presence of neuroendocrine marker in pulmonary adenocarcinoma seems to be associated with increased sensitivity to chemotherapy.