Is Helicobacter pylori a Poor Prognostic Factor for HER-2 SISH Positive Gastric Cancer?

Selcukbiricik, Fatih,Tural, Deniz,Erdamar, Sibel,Buyukunal, Evin,Demirelli, Fuat,Serdengecti, Suheyla Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Background: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown. Materials and Methods: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated. Results: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes. Conclusions: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.

Is Her-2 Status in the Primary Tumor Correlated with Matched Lymph Node Metastases in Patients with Gastric Cancer Undergoing Curative Gastrectomy?

Selcukbiricik, Fatih,Erdamar, Sibel,Buyukunal, Evin,Serrdengecti, Suheyla,Demirelli, Fuat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05).Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

Clinicopathological Features and Localization of Gastric Cancers and their Effects on Survival in Turkey

Selcukbiricik, Fatih,Tural, Deniz,Bilici, Ahmet,Uzel, Esengul Kocak,Ozguroglu, Mustafa,Demirelli, Fuat,Buyukunal, Evin,Serdengecti, Suheyla Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. Materials and Methods: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. Results: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. Conclusions: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

Perineural Invasion Independent Prognostic Factors in Patients with Gastric Cancer Undergoing Curative Resection

Selcukbiricik, Fatih,Tural, Deniz,Buyukunal, Evin,Serdengecti, Suheyla Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Methods: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. Conclusions: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.

Male Breast Cancer: 37-Year Data Study at a Single Experience Center in Turkey

Fatih Selcukbiricik,Fatih Aydoğan,Nuran Beşe,Evin Büyükünal,Süheyla Serdengeçti,Deniz Tural 한국유방암학회 2013 Journal of breast cancer Vol.16 No.1

Purpose: The aim of this study is to evaluate the effects of prognostic factors on the overall survival (OS) and locoregional control (LC) among male breast cancer (MBC) patients treated at Cerrahpasa Medical School Hospital, along with a review of the related literature. Methods: The data of 86 patients treated for MBC from 1973 to 2010 are retrospectively reviewed. Patient demographics and clinical information, including the date of diagnosis, treatment, clinical course, and the date and causes of death are routinely recorded. Results: Median follow-up was 66 months. Isolated local-regional recurrence and distant metastases were observed in 15 (17.4%) and 24 (34.1%) of the cases, respectively. The 5-year OS rate was 65.8%; the disease-free survival rate was 72.4%, and the LC rate was 89.7%. The prognostic factors influencing local relapse were the T stage (p=0.002) and the chest wall muscular invasion (p=0.027) in the univariate analysis. The prognostic factors influencing OS were the presence of a positive axillary lymph node (p=0.001) and the T stage (p=0.001) in the univariate analysis. The T stage (p=0.008) and node (N) stage (p=0.038) were significant prognostic factors for OS in the multivariate analyses. Also, the T stage (p=0.034) was found to be significant for LC. Conclusion: We found that only the tumor size and lymph node status were independent prognostic factors for survival. In addition, only the tumor size was an independent prognostic factor for locoregional relapse. Modified radical mastectomy and conservative surgical procedures had similar outcomes for LC.

Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

Bilici, Ahmet,Selcukbiricik, Fatih,Demir, Nazan,Ustaalioglu, Bala Basak Oven,Dikilitas, Mustafa,Yildiz, Ozcan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.