• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6109-6113
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• 2014

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.162-172
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• 2017

Purpose: Previous studies indicated conflicting results regarding the prognosis of gastric cancer with a family history (FHX). This study aimed to determine the clinicopathological features and survival of patients with gastric cancer with a FHX. Materials and Methods: We reviewed 2,736 patients with gastric cancer who underwent surgery between 2003 and 2009. The prognostic value of a FHX was determined in the multivariate model after adjusting for variables in the Asian and internationally validated prognostic models. Results: Of the patients, 413 (15.1%) had a FHX of gastric cancer. The patients with a FHX were younger (58.1 vs. 60.4 years; P<0.001) than the patients without a FHX. There were no significant differences in the histopathological characteristics between the 2 groups. A FHX was associated with a better overall survival (OS) rate only in the stage I group (5-year survival rate, 95% vs. 92%; P=0.006). However, the disease-specific survival (DSS) rate was not significantly different between the 2 groups in all stages. The multivariate model adjusted for the variables in the Asian and internationally validated prognostic models revealed that FHX has no significant prognostic value for OS and DSS. Conclusions: The clinicopathological features and survival of the patients with gastric cancer with a FHX did not significantly differ from those of the patients without a FHX.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1375-1379
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• 2014

Background: Differences in clinicopathological characteristics of gastric cancer (GC) between young and older patients are controversial and a matter of debate. Determining the statistical significance of clinicopathological information with respect to age might provide clues for better management and treatment ofGC. Materials and Methods: A total ofl03 Indiao GC patients were enrolled for study and specimens were classified according to the AjCC-TNM system. Patients were grouped into two age-wise categories, young patients (<40 years; n=13) and older patients (${\geq}40$ years, n=90). The clinicopathological features of both groups were retrospectively examined and compared. p53 alterations were analyzed by polymerase chain reaction-single strand conformational polymorphism and immunohistochemistry methods at gene and protein levels respectively. The cases were considered p53 over-expressed if it was present in more than 25% of the tumor cells and p53 alterations was correlated with the clinicopathological characteristics of the patients as well as etiological factors for GC in both groups. Results: We found significant association of young patients with cancer stage (p=0.01), and very strong association with histology grade (p=0.064) and poorly differentiated (p=0.051) state of GC. However, neither young nor elderly patients showed associations with location, gender, etiological factors and p53 expression and alteration. Overall the male-to-female ratio of GC patients was 3.12 and the value was higher in the young (5.5) than in the older group (2.91). Conclusions: Clinicopathological features of GC like caocer stage, cell differentiation and histological grades were significantly different among young and old age cohorts. We observed a male predominance among the young group that decreased significantly with advancing age. More awareness of GC onset is required to detect cancer at an early stage for successful treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8367-8370
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• 2014

The relationship between caveolin-1 (Cav-1) and clinicopathological characteristics of gastric cancer is controversial, although Cav-1 plays an important role in tumor metastasis. To evaluate the clinicopathological and prognostic value of expression in patients with gastric cancer, a meta-analysis was performed to investigate the impact on clinicopathological parameters and prognosis in gastric cancer cases. Studies assessing these parameters for Cav-1 in gastric cancer were identified up to June 2014. Finally, a total of six studies met the inclusion criteria. Our combined results showed that Cav-1 expression was significantly associated with the Lauren classification (pooled OR=0.603, 95% CI: 0.381-0.953, P=0.030). Furthermore, we found that Cav-1 expression predicted a better overall survival in gastric cancer patients (pooled OR=0.590, 95% CI: 0.360-0.970, P=0.038, fixed-effect). In conclusion, the overall data of the present meta analysis showed that Cav-1 expression was not correlated with clinicopathological features except for the Lauren classification. Simultaneously, Cav-1 overexpression predicted a better overall survival in gastric cancer. Cav-1 expression in tumors is a candidate positive prognostic biomarker for gastric cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3705-3709
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• 2013

Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2587-2592
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• 2016

Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ${\leq}45$ years) with controls (>45 years). Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features. Results: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls. Conclusions: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.23-30
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• 2011

Purpose: ${\alpha}$-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis. Materials and Methods: Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed. Results: There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP-negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP-positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP-positivity to be the independent prognostic factors. Conclusions: AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6415-6421
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• 2012

Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1643-1649
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• 2015

Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/amplified (HER2+), the efficacy of trastuzumab treatment and survival results. Materials and Methods: Patients with HER2-positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. Conclusions: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.