Comparison of Pathological Prognostic Stage and Anatomic Stage Groups According to the Updated Version of the American Joint Committee on Cancer (AJCC) Breast Cancer Staging 8th Edition.

BACKGROUND We compared pathological prognostic stage (PPS) with anatomic stage (AS) groups according to the updated version of breast cancer staging of the American Joint Committee on Cancer (AJCC) 8th Edition. MATERIAL AND METHODS We evaluated 353 breast cancer patients initially treated with surgery. AS and PPS were performed by evaluating the pathological data of the patients according to the AJCC 8th Edition breast cancer updated version. Stages and survival rates between the 2 staging systems were evaluated and compared. Disease-free survival (DFS) and disease-specific survival (DSS) were calculated according to both staging systems using Kaplan-Meier test. After the PPS change was made in each AS group, 10-year DFS and 10-year DSS of the changed groups were compared using the chi-square test. RESULTS The median follow-up was 114 months and the median age was 48 years. In 192 (54.4%) patients the stage change. The most significant change was 1-level downstaging in 70 (22.4%) patients, and 2-levels downstaging in 78 (22.1%) patients. Five-year DFS, 10-year DFS, 5-year DSS rate, and 10-year DSS were 86.3%, 80.3%, 93.8%, and 84.1%, respectively. The PPS system was found to provide better prognostic information when the patients with AS IIB and IIIA groups were compared according to the PPS. CONCLUSIONS According to the updated version of the AJCC 8th Edition, half of our patients had stage change when they were evaluated according to AS and PPS system. PPS gives better information about prognosis than does AS.

Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

AIMS: The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. METHODS: In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. RESULTS: In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. CONCLUSIONS: We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma.

[Investigation of Chlamydia trachomatis seropositivity in patients with cervical cancer]. / Servikal Kanserli Hastalarda Chlamydia trachomatis Seropozitifliginin Arastirilmasi

Chlamydia trachomatis is the most frequent bacterial pathogen causing sexually transmitted diseases worldwide. Many studies emphasize that chlamydial infections may play role as a cofactor in cervical cancers caused by high risk human papillomavirus types. The aim of this study was to investigate the presence of antibodies specific for C.trachomatis in patients with cervical cancer in order to detect the frequency of chlamydial infections. A total of 77 patients diagnosed as cervical cancer who have undergone surgery and on treatment at Oncology Institute of Istanbul Faculty of Medicine were included in the study, together with 20 healthy women as the control group. Serum samples obtained from patient and control groups were investigated by a commercial microimmunofluorescence kit (Orgenium Laboratories, Finland) for the detection of C.trachomatis IgG, IgA and IgM antibodies. All of the control subjects (mean age: 30.25 ± 6.4 years) were found seronegative, however the seropositivity rate detected in patients with cervical cancer was 9.1% (7/77). Serological data were interpreted as previous infections in four patients with single IgG positivity (titers: 1/16 in three and 1/32 in one patient), acute infections in two patients with IgG + IgM positivity (titers: IgG 1/64 and IgM 1/64 for both patients), and chronic infection in one patient with IgG + IgA positivity (titers: IgG 1/128 and IgA 1/20). The mean age of seven seropositive patients was 53.88 ± 12.1 years, and three of them had antibodies against FGK, three against BDE and one against CHIJ serogroups of C.trachomatis. None of the cases had the history of sexually transmitted disease. No statistically significance was found between patient and control groups regarding C.trachomatis IgG, IgA and IgM seropositivity (for IgG; p= 0.339, for IgA; p= 1.000, for IgM; p= 1.000). However, it was thought that the statistical evaluations may not be conclusive due to the small number of study groups. In conclusion further studies with large numbers of cases are needed to understand the role of chlamydia infections in the development of cervical cancer.

Pushing the Limits of Breast-Conserving Surgery with Extreme Oncoplasty.

Introduction: We aimed to report the long-term surgical outcomes of extreme oncoplasty techniques in selected patients with unifocal (UF)/cT3 or multifocal-multicentric tumors (MFMC). Material and Methods: Patients who were initially recommended to have mastectomy underwent extreme oncoplastic breast-conserving surgery (eOBCS) including therapeutic reduction mammoplasty, racquet, and round-block mammoplasty, Grisotti flap, or combined technique were included. Preoperative tumor parameters, clinical outcomes, rate of local recurrence, survival, and patients' satisfaction were assessed. Results: Eighty-six patients with a median age of 51 years were followed for a median follow-up of 75 (8-154) months; 31 (36%) had cT3 and 55 (64%) had MFMC tumors. The majority of patients (83.6%) had invasive cancer. The median UF tumor size was 58 mm (range 51-100) on imaging and 51 mm (range 50-60) on final pathology. The median tumor span for MFMC was 65 mm (range 53-95) on imaging, whereas the median of the largest tumor size was 30 mm (range 22-60) on final pathology. Seventy-one patients (82.5%) were ER-positive, 17 (19.7%) were HER2 positive, and 8 (9.3%) were triple-negative breast cancer. Four patients (4.7%) required further intervention for having positive margins (3 re-excisions, 1 completion mastectomy). Three local recurrences (3.4%) and 10 (11.6%) distant metastasis occurred. The cosmetic outcome was excellent in 37 (43%) patients. No major complications were observed. Conclusions: eOBCS can be a good option for patients who initially require mastectomy. Appropriate patient selection, a multidisciplinary approach, and patient consent are essential steps of the procedure.

Clinicopathologic characteristics and prognostic factors in patients with male breast cancer: A single tertiary center experience.

BACKGROUND: The goal of this study was to assess the clinicopathologic characteristics and prognostic variables in men with breast cancer (BC). METHODS: Clinical features, pathological characteristics, stage at diagnosis, and therapy data were noted. Survival analysis was performed using the log-rank technique and Cox regression model. RESULTS: Eighty patients were included in the study. In 31% of the individuals, BRCA (BReast CAncer genes 1 and 2) mutations were identified. The estrogen receptor (ER) positivity ratio was 93.6%, whereas the progesterone receptor (PR) positivity ratio was 74.4%. In 16.9% of the cases, HER2 overexpression was found. The median survival time was 120.9 months (70.3-171.5), and the five-year overall survival (OS) ratio was 74.9%. In univariate analysis, BRCA mutation status had no effect on OS (P = 0.50). CA15-3 levels (P = 0.03) at diagnosis and history of smoking (P = 0.03) were significantly linked with OS. However, the multivariate analysis could not confirm these results. CONCLUSIONS: We found that BRCA mutation, body mass index, a history of smoking, and alcohol consumption did not affect the OS in this research.

Long-term outcomes and predictors of recurrence in node-negative early stage breast cancer patients.

BACKGROUND: We evaluated the outcomes, and risk factors for recurrence in patients with early stage node-negative breast cancer in this study. METHOD: Retrospective data analysis was done on patient treatment records from 1988 to 2018. The patient's demographic, clinical, pathological, and therapeutic characteristics were noted. To evaluate survival analysis and predictors of recurrence, we employed Kaplan-Meier analysis with the log-rank test. RESULTS: A total of 357 patients in all were enrolled in the research. At the time of diagnosis, the median age was 50 (with a range of 18-81). A total of 85.5% of patients had undergone a lumpectomy, while 14.5% had a mastectomy. 78.7% of patients had sentinel lymph node biopsy, and 21.3% had axillary lymph node dissection. In addition, the patients received adjuvant radiotherapy (88.7%), adjuvant endocrine therapy (82.1%), and adjuvant chemotherapy (48.5%). Recurrence of the tumor occurred in 31 (8.7%) patients (local recurrence 45.2% and metastatic disease 54.8%). Ten- and twenty-year recurrence-free survival rates were 92% and 77%. 19 (5.3%) patients had also developed contralateral breast cancer. Ten-year survival rates were 91.6%, and 20-year survival rates were 76.6%, respectively. Aged over 65 years (p = 0.004), necrosis (p = 0.002), mitosis (p = 0.003), and nuclear pleomorphism (p = 0.049) were found as statistically significant factors for recurrence in univariate analysis. In the ROC analysis, the largest size of the tumor (over 1.45 cm, p = 0.07) remained outside the statistical significance limit in terms of recurrence. CONCLUSIONS: Thirty-year outcomes in individuals with early stage, node-negative breast cancer were shown in this study. We found that the recurrence ratios between 10 and 20 years were more frequent than the first 10 years during the follow-up. Despite the small number of patients who experienced a recurrence, we demonstrated that, in univariate analysis, being older than 65 and having some pathological characteristics (nuclear pleomorphism, mitosis, and necrosis) were statistically significant factors for disease recurrence.

Association of coping style, cognitive errors and cancer-related variables with depression in women treated for breast cancer.

OBJECTIVE: The purpose of this study was to examine the correlation between depression levels with coping styles and cognitive errors in women treated for breast cancer. METHODS: A total of 110 breast cancer outpatients who had had surgery at least 6 months previously, had completed adjuvant cancer treatment and had not experienced metastasis or recurrent lesions were evaluated. The Automatic Thoughts Questionnaire, Cognitive Errors Questionnaire, Mental Adjustment to Cancer Scale and Beck Depression Inventory were administered to all patients. Semi-structured interview forms were used to obtain medical and demographic data. All patients were categorized into depression and non-depression groups according to their Beck Depression Inventory scores. The study protocol was approved by the Medical Ethics Committee of Istanbul University Oncology Institute. RESULTS: Higher cognitive errors and automatic thought scores were found in the depression group. Fighting spirit was found to be the primary coping style used in the non-depression group, while helplessness/hopelessness, anxious/preoccupation and fatalism were the coping styles used the most in the depression group. No association between depression and socio-demographic (except for educational level) and cancer-related variables was detected. However, it was found that automatic thoughts, cognitive errors, education level, fighting spirit and anxious/preoccupation are important indicators of depression in our sample. CONCLUSIONS: A causal relationship exists between depression and a patient's cognitive patterns and accompanying anxiety. The degree of depression is inversely related to both fighting spirit coping type and educational level. If clinicians take this into consideration, diagnosing and treating depression will be more effective.

Is Surgical Treatment an Option for Locally Advanced Cervical Cancer in the Presence of Central Residual Tumor after Chemoradiotherapy?

OBJECTIVE: To evaluate the outcomes of surgical treatment in patients with chemoradiotherapy (CRT)-resistant and locally advanced cervical cancer (LACC). METHODS: Patients with LACC who underwent surgery due to resistance to CRT between 2005 and 2015 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) related factors were analyzed. RESULTS: A total of 23 patients were included in the study and the median age was 51 years old. A total of 14 patients (60.8%) experienced recurrence; among these recurrences, 8 of them were local, 5 were distant, 1 was both distant and local. A total of 9 patients (39%) died. The Median DFS and OS durations were 15 and 32 months, respectively. A total of 17 patients (74%) had undergone simple hysterectomy, 4 (17%) radical hysterectomy, and 2 (9%) total pelvic exenteration. Postoperative grade 3 and 4 complications were seen in 12 patients (52%). Macroscopic tumor presence in the pathology specimen was associated with distant recurrence and positive surgical margins with local recurrence (Log-Rank test p = 0.029 and p = 0.048, respectively). The only factor associated with OS was surgical margin positivity (Log-Rank test p = 0.008). The type of surgery, grades 3 and 4 postoperative complications, brachytherapy, and tumor histology were not associated with recurrence. CONCLUSION: In patients with LACC, hysterectomy is an option in the presence of a central residual tumor after CRT. However, the risk of grades 3 and 4 complications of performed surgery is high. The presence of macroscopic tumor in the pathology specimen and positive surgical margins are poor prognostic factors. The goal of the surgeon should be to achieve a negative surgical margin. It does not seem important if the surgery is simple or radical.

Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis.

BACKGROUND: To identify the candidates for prophylactic cranial radiotherapy (PCI) among the patients with early and advanced-stage breast cancer. METHODS: The demographic, pathologic and clinical features and survival results of 182 brain metastatic breast cancer patients treated with cranial radiotherapy were examined. RESULTS: Early stage patients who progressed with isolated brain metastasis had longer survival (13 months vs. 4 months P = 0.006). Lobular/mixed type histology (P = 0.033), high nuclear (P = 0.046) and high histological grade (P = 0.034) were the prognostic factors for isolated brain metastases. The most significant factor for the time to brain metastasis was the number of involved of lymph nodes (P = 0.004). In 60% of 148 patients with metastatic breast cancer, a progression with isolated brain metastasis was developed while the systemic disease was under control. Isolated brain metastasis progression was related to the presence of the hepatic metastasis at the first relapse (P = 0.001) and with ErbB-2 overexpression (P = 0.034). The time to the brain metastasis from the first extracerabral metastasis was associated with the high nuclear grade (P = 0.040) and with chemoresistance (P = 0.037). The median survival time after the brain metastases in chemosensitive patients was longer than in chemoresistant patients (8 months vs. 3 months P = 0.044). In chemoresistant patients (P = 0.0028) and/or in triple negative patients (P = 0.05) the development of the brain metastasis was early and the survival after brain metastasis was short. DISCUSSIONS: Since there is a tendency to early brain metastasis in early stage patients with high-grade, lobular/mixed type histology tumors and with a high number of involved lymph nodes, the value of PCI can be explored in these patients by a well designed prospective trial. Advanced stage chemosensitive patients with ErbB-2 over-expression and/or with hepatic metastasis at their first relapse may be candidates for PCI. There is no place for PCI in chemoresistant and triple-negative breast cancer patients.

Breast cancer and cyclin D1 gene polymorphism in Turkish women.

BACKGROUND: Cyclin D1 protein plays an important part in regulating the progress of the cell during the G(1) phase of the cell cycle. It has been suggested that G870A polymorphism at the exon4/intron4 splicing region of the CCND1 gene may play a role in tumorigenesis and invasiveness. PATIENTS AND METHODS: A case-control study was performed to test the association between G870A polymorphisms in the CCND1 gene and breast cancer risk and cancer progression. For this purpose, 38 patients with breast cancer and 64 healthy women controls were included in the study. The CCND1 G870A polymorphisms in our study groups were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using peripheral blood samples. RESULTS: A significant difference was found in the distribution of the GG, AG and AA genotypes between the patient group and the control group (p=0.021). A lower risk (odds ratio 0.435, 95% confidence interval 0.223-0.846) was found to be associated with heterozygote AG individuals when compared with homozygote allele carriers in breast cancer. The cyclin D1 A870G genotype was associated with capsular invasion (p=0.02). CONCLUSION: The risk of breast cancer development and prognosis may be associated with genetic variation in the CCND1 genotype, which may be used as a biomarker for further studies.

Survival Impact of Optimal Surgical Cytoreduction in Recurrent Epithelial Ovarian Cancer with Brain Metastasis.

AIM: The aim of this study was to determine the clinicopathological characteristics, treatment details and outcome of patients with brain metastasis from epithelial ovarian carcinoma (EOC). METHODS: This study included 21 patients diagnosed with brain metastasis from EOC between 1999 and 2009. RESULTS: Median age was 61 years (range 38-77). The median time elapsed from EOC diagnosis to brain metastasis detection was 32 months. Single brain metastases were found in 10 (48%) cases, and there was extra-cranial disease in 11 (52%) cases. During the mean 86 months of follow-up, 18 of the patients (86%) died of the disease and 3 (14%) were alive with disease. The median survival time after the initial diagnosis of brain metastasis was 9 months. The median overall survival (OS) from initial diagnosis of EOC was 50 months. In univariate analysis, prolonged time from initial diagnosis to central nervous system metastasis (more than 32 months) (p = 0.001), treatment with radiotherapy (p < 0.001), optimal cytoreductive operation (p = 0.02) were all positively correlated with OS. CONCLUSION: The prognosis of patients with brain metastasis from EOC is still poor. The significant predictors of survival in our series were whole brain radiotherapy, prolonged elapsed time from initial diagnosis to brain metastasis and optimal cytoreductive surgery.

Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer.

OBJECTIVE: The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinely investigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was to evaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 and BRCA2 testing in Turkey. MATERIALS AND METHODS: The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for both small indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) in patients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breast cancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer. CONCLUSIONS: Rearrangements were found with high rates and were strongly associated with bilateral and triple-negative status of patients with breast cancer, which are signs of high risk for breast and ovarian cancer. Analysis of rearrangements should definitely be included in routine clinical practice in Turkey for high-risk families and also for improved cancer risk prediction for families.

Favorable Outcome with Close Margins in Patients Undergoing Nipple/Skin Sparing Mastectomy with Immediate Breast Reconstruction: 5-year Follow-up.

BACKGROUND: Implant-based breast reconstruction after mastectomy has recently been reported to be the preferred type of surgery among breast-specific surgeons and plastic surgeons. AIMS: To explore the significant clinicopathological factors associated with long-term outcome related to local recurrences of the nipple among patients who underwent immediate breast reconstruction with tissue expander or implant after mastectomy. STUDY DESIGN: Retrospective cohort. METHODS: From January 2007 to January 2013, 51 breast cancer patients who underwent immediate breast reconstruction with tissue expander or implant were retrospectively analysed. Patients' demographic data, clinicopathological characteristics, and clinical outcome by disease-free survival and disease-specific survival analyses were determined. RESULTS: The median follow-up was 64 (31-114) months. Of the 57 mastectomies, 41 were skin sparing mastectomy (72%) and 16 were nipple-areola sparing mastectomy (28%). Immediate breast reconstruction surgery included tissue expander (n=46, 81%) or implant (n=11, 19%) placement. The molecular subgroups of 47 invasive cancers were as follows: luminal A (n=23, 49%), luminal B (n=16, 34%), non-luminal HER2 (n=5, 10.6), triple negative breast cancer (n=3, 6.4%). The 5-years disease-specific survival, disease-free survival, and locoregional recurrence-free survival rates were 96.8%, 90%, and 97.6% respectively. Patients with luminal A cancer were found to have an improved 5-year disease-free survival time than other (luminal A; 100% vs. non-luminal A; 78%; p=0.028). Of the 14 nipple-areola sparing mastectomy, 13 had a close median tumour distance to nipple-areola complex (<20 mm) with a 5-year locoregional recurrence free survival of 100%. CONCLUSION: Immediate breast reconstruction with implant or tissue expander can be safely applied in patients undergoing skin sparing mastectomy or nipple-areola sparing mastectomy. Patients with luminal-A type show the most favourable outcome. During the 5-year follow-up period, patients even with close margins (<20 mm) to nipple-areola complex with nipple-areola sparing mastectomy have excellent locoregional and overall survival when treated by contemporary multidisciplinary oncological management.

Effect of the childhood trauma on the adjustment to cancer in the patients with breast cancer.

BACKGROUND: Early identification of patients coping poorly is important for compliance with treatment and control of distress. This study aims to investigate the effect of the childhood trauma experience on the type of reaction and adjustment that the person exhibits to the cancer among the patients with breast cancer. METHODS: This cross-sectional study enrolled 310 patients with breast cancer. The effect of the childhood trauma and the psychological condition on the adjustment to cancer was investigated by assessing the adjustment to cancer, the experiences of childhood trauma and psychological status of the subjects using mental adjustment to cancer scale (MAC), childhood trauma questionnaire (CTQ28), Beck Depression Inventory (BDI) and Beck anxiety inventory (BAI). RESULTS: Majority of the subjects (77.4%) showed positive adjustment to cancer. Fighting spirit (63.9%) was the most commonly seen mechanism of adjustment to cancer. Of the subjects, 54.5% suffered at least one of the childhood trauma types. Among the patients, 47.1% had depression and 58.4% had anxiety. In the multivariate logistic regression analysis, emotional neglect and depression, respectively, have an effect on both positive and negative adjustment to cancer. CONCLUSIONS: Our study demonstrated that childhood trauma, especially emotional neglect, affects coping and adjustment among the patients with breast cancer. It is necessary to determine the childhood experiences to ensure the development of psychosocial interventions that will increase the adjustment and quality of life after the diagnosis of the cancer.

High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium: An immunohistochemical and clinicopathologic study.

Undifferentiated/dedifferentiated endometrial carcinomas (UCE/DCEs) of the endometrium are rare tumors with poor prognosis. There are few clinicopathologic studies with detailed immunohistochemical analysis regarding UCE/DCEs.We evaluated the diagnostic value of a selected tumor stem-cell marker and epithelial-mesenchymal transition (EMT) markers, in addition to previously studied markers in identifying UCE/DCEs from other types of high-grade endometrial carcinomas.Eleven cases of UCE/DCEs with complete clinical follow-up that were diagnosed between 2006 and 2015 were included in the study. For immunohistochemical comparison, 11 clinically matched cases for each type of other high-grade endometrial carcinomas (high-grade endometrioid (F3-EC), serous [SC], and clear cell carcinoma [CCC]) were used as a control group. An immunohistochemical analysis including fascin, SALL4, E-cadherin, and ß-catenin, in addition to epithelial and neuroendocrine markers was performed in each case.The majority of UCE/DCEs displayed diffuse expression of fascin (81.9%) and loss of E-cadherin expression (54.5%). SALL4 expression was detected in 36.3% of the UCE/DCE cases. SALL4 expression was significantly more frequent in UCE/DCEs than all other high-grade carcinomas (P < 0.001). Loss of E-cadherin and fascin expression was significantly more frequent in UCE/DCEs than high-grade endometrioid and clear cell adenocarcinomas (P = 0.012, 0.014 and P = 0.01, 0.003, respectively).We suggest that loss of E-cadherin expression together with fascin and SALL4 immunopositivity in addition to morphologic features have an impact in differential diagnosis of UCE/DCEs from other high-grade endometrial carcinomas.

Are CYP17 genotypes a biomarker for ovarian cancer in patients with cancer history in their family?

BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases. However, the vast majority of ovarian and breast cancer cases do not display the hereditary form of the disease. Estrogen-metabolizing genes may also contribute to the predisposition of breast or ovarian cancer. Polymorphic variants of the estrogen-metabolizing gene, CYP17, have been associated with the risk of hormone-related cancers. In this study we investigated the CYP17 polymorphisms in ovarian cancer patients harboring mutations in the BRCA1 and BRCA2 genes, patients displaying familial characteristics but not carrying mutations and patients with sporadic ovarian cancer. Association between the allele frequencies, the CYP17 genotype and tumor characteristics or clinical parameters was evaluated. Our data suggest evidence for an association between ovarian cancer risk and the CYP17 genotype in the subgroup of patients with familial disease in whom no mutations in the BRCA genes are found. Although there were no statistically significant differences in the genotype distribution between the control group and the subgroup of patients with BRCA mutations, the frequency of the CYP17 A2 allele was significantly higher in the subgroup of patients without BRCA mutations. We found a four- to eightfold higher risk in ovarian cancer patients with family history but without BRCA mutations. Our data indicate that the CYP17 A2 allele polymorphism may confer an increased risk and can provide a biomarker for ovarian cancer patients in whom no mutations in the BRCA genes are observed.

Evaluation of prognostic factors and comparison of systemic treatment modalities in patients with recurrent or metastatic endometrial carcinoma.

BACKGROUND: Prognostic factors related to survival in patients with inoperable metastatic or recurrent endometrial carcinoma (MREC) have remained unclear due to lack of clinical trials. The management of these patients is also controversial. This study was performed to compare the efficacy and toxicity profiles of two different systemic therapies (chemotherapy vs hormonal therapy) given for the treatment of patients with MREC and to identify the impact of various prognostic factors on the survival. METHODS: Between 1992 and 2004, 44 patients with MREC were admitted to our oncology department. Four cases were excluded from this retrospective study because of lack of data in their charts. Age, presence of other systemic diseases (such as diabetes mellitus, hypertension), histological type, tumor grade, stage, disease-free interval, site of recurrence or metastasis, systemic treatment modality, overall response to treatment, and duration of time to progression were evaluated as prognostic factors. Cox regression analysis was performed for identification of independent prognostic factors and differences between patients characteristics of two treatment groups were calculated by the chi-square or t test. RESULTS: The median follow-up was 18 mo (range 3-113). The overall response rates for chemotherapy and hormonal therapy group were 42% and 41%, respectively (p > 0.05). The median time to progression was 4 mo for the chemotherapy group and 5 mo for the hormonal therapy group (p > 0.05). The median survival after metastasis or recurrence was 11 mo for the chemotherapy group and 16 mo for the hormonal therapy group (p > 0.05). In the group of chemotherapy, grade 3-4 hematologic and nonhematologic toxicities were seen in eight and two, patients, respectively. No grade 3-4 toxicities were noted in patients treated with hormonal therapy. In multivariate analysis, only time to progression (p=0.001) and grade (p=0.04) were the independent prognostic factors on survival after metastasis or recurrence. CONCLUSION: Histological differentiation and duration of time to progression are predictive factors for survival after metastasis or recurrence in the whole group. The efficacy of two different groups of treatment in these patients appears to be similar. But the chemotherapy may have some disadvantageous in terms of toxicity. This study supports a future randomized prospective trial of hormonal therapy vs chemotherapy in patients with MREC.

Is surgical treatment an option for locally advanced cervical cancer in the presence of central residual tumor after chemoradiotherapy?

Abstract Objective To evaluate the outcomes of surgical treatment in patients with chemoradiotherapy (CRT)-resistant and locally advanced cervical cancer (LACC). Methods Patients with LACC who underwent surgery due to resistance to CRT between 2005 and 2015 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) related factors were analyzed. Results A total of 23 patients were included in the study and the median age was 51 years old. A total of 14 patients (60.8%) experienced recurrence; among these recurrences, 8 of them were local, 5 were distant, 1 was both distant and local. A total of 9 patients (39%) died. The Median DFS and OS durations were 15 and 32 months, respectively. A total of 17 patients (74%) had undergone simple hysterectomy, 4 (17%) radical hysterectomy, and 2 (9%) total pelvic exenteration. Postoperative grade 3 and 4 complications were seen in 12 patients (52%). Macroscopic tumor presence in the pathology specimen was associated with distant recurrence and positive surgical margins with local recurrence (Log-Rank test p = 0.029 and p = 0.048, respectively). The only factor associated with OS was surgical margin positivity (Log-Rank test p = 0.008). The type of surgery, grades 3 and 4 postoperative complications, brachytherapy, and tumor histology were not associated with recurrence. Conclusion In patients with LACC, hysterectomy is an option in the presence of a central residual tumor after CRT. However, the risk of grades 3 and 4 complications of performed surgery is high. The presence of macroscopic tumor in the pathology specimen and positive surgical margins are poor prognostic factors. The goal of the surgeon should be to achieve a negative surgical margin. It does not seem important if the surgery is simple or radical.

Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ±â€Š9% vs. 82 ±â€Š6%, P = 0.013) and overall survival (OS) (68 ±â€Š8% vs. 94 ±â€Š4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.