Omer Fatih Olmez

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome

IntroductionThe identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour.AimWe sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC.Material and methodFormalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis.ResultsA total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression-free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05).ConclusionThis study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.

Clinical significance of adiponectin expression in colon cancer patients

PURPOSE Surgery is the definitive treatment for early colon cancers. Adjuvant therapies are used with the aim of eradicating micrometastases and improving cure rates. Recent studies have proposed that adiponectin might be responsible for obesity-related malignancies. We investigated the prognostic value of this cytokine. MATERIALS AND METHODS Patients who underwent surgical removal of stage II or III (TNM staging) primary tumors and were followed for at least three years were included in the study given adequate specimen for immunohistochemical evaluation. Based on these criteria, 53 patients were included. RESULTS Mean age was 58.3 ± 10.1 years (35-78 years). The mean follow-up time was 41 months (10-96 months). Immunohistochemical evaluation identified 21 patients (39.6%) with cytoplasmic adiponectin present in their specimens. The rates of recurrence were 42.9% (9/21) and 34.4% (11/32) in patients with and without adiponectin expression, respectively. In cases with adiponectin expression, mean disease - free survival was 60.3 ± 9.03 months, and in cases without adiponectin expression, mean disease - free survival was 68.7 ± 6.67 months (P = 0.414). Mean overall survival of patients with adiponectin expression was 65 months compared to 67 months for patients without (P = 0.786). CONCLUSION Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

Clinical outcomes of lung metastasectomy in patients with colorectal cancer

AIM To investigate prognostic factors of survival following curative, non-palliative surgical removal of lung metastases secondary to colorectal cancer (CRC). METHODS Between 1999 and 2009, a radical metastasectomy with curative intent was performed on lung metastases in 21 patients with CRC (15 male and 6 female; mean age: 57.4 ± 11.8 years; age range: 29-74 years) who had already undergone primary tumour resection. RESULTS The mean number of lung metastases ranged from one to five. The mean overall survival was 71 ± 35 mo (median: 25 mo). After adjusting for potential confounders, multivariable Cox regression analyses predicted only the number of lung metastases (1 vs ≥ 2; hazard ratio: 7.60, 95% confidence interval: 1.18-17.2, P = 0.03) as an independent predictor of poor survival following lung resection for metastatic CRC. CONCLUSION Resection of lung metastases is a safe and effective treatment in selected CRC patients with single lung metastases.

Prognostic Significance of Human Epidermal Receptor (HER)- 3 Immunohistochemical Expression in Patients with Metastatic Breast Cancer

BACKGROUND Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. METHODS We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. CONCLUSIONS HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.

Malignant melanoma of the stomach in an elderly patient.

To the Editor, Malignant melanoma (MM) is a highly aggressive disease that originates from typical sites where the melanocytes can be usually found (skin, eyes, meninges, and anal region) (1,2). MM can attack any part of the gastrointestinal (GI) tract, and this event is mainly caused by metastatic spread from primary cutaneous lesions. However, there is a portion of GI melanomas without any documented evidence of a primary lesion in the skin or elsewhere, even after thorough examination. In such cases, involved organ of the digestive system is considered the primary site of MM (2,3).

Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer.

Introduction Triple-negative breast cancers (TNBCs) – which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) – have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. Material and methods Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. Results Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. Conclusions Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology.

Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus–myoclonus–ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%–25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.

Should Patients be Routinely Screened for Hepatitis BSerology before the Use of Chemotherapy Due to SolidOrgan Tumors

Background: The prevalence of chronic hepatitis-B virus (HBV) is highly variable by region in the world. In chronic HBV, most of exacerbations are associated with the interaction of immune response to HBV and virus replication. All kinds of chemotherapy regimens potentially cause HBV replication. Case Report: 58-year-old male patient, non-small cell lung adenocarcinoma was diagnosed. Adjuvant chemotherapy combination including navelbine and cisplatin was initiated for the patient. He admitted with the complaints of weakness and fatique after the one week of the second cure of chemotherapy. On physical examination, oral mucosa, sclera and skin were icteric. HBV-DNA level was measured as > 1000000000 (1 billion) IU/ mL. Conclusion: Clear benefit or harm of routine hepatitis B screening is controversial during the use of chemotherapy in solid organ tumours. Especially in our country in which HBV prevalence is high, HBV infection screening have to be considered in patients scheduled to receive chemotherapy due to solid organ tumours in terms of HBV reactivation.

Patients with HER2-positive early breast cancer receiving adjuvant trastuzumab: clinicopathological features, efficacy, and factors affecting survival.

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.

The SOCS-1 -1478CA/del Polymorphism is not Associated with Colorectal Cancer or Age at Onset in Turkish Subjects

BACKGROUND Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS- 1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. MATERIALS AND METHODS A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. CONCLUSIONS The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.