Investigation of the Relationship Between Tumor Microenvironment and Prognostic Parameters in Invasive Breast Carcinomas of No Special Type: A Retrospective Analysis.

OBJECTIVE: The tumor microenvironment is a heterogeneous and constantly changing territory that plays an active role in tumor formation and progression. It constantly interacts with tumor cells, plays an active role in tumor development, and even appears as a parameter of prognostic importance, and the importance of the tumor microenvironment in breast cancer has been emphasized by recent studies. In this study, we aimed to retrospectively evaluate the relationship between the tumor microenvironment and prognostic parameters in invasive breast carcinomas of no special type. MATERIAL AND METHODS: A total of 271 cases diagnosed as invasive breast carcinoma of no special type from resection materials in our center between 2007 and 2015 were included in the study. Hematoxylin-eosin stained slides with a thickness of 4-5 micrometers were evaluated in terms of tumor infiltrating lymphocytes, peritumoral and intratumoral desmoplastic reaction, intratumoral and peritumoral tumor budding, stromal features, and tumor growth pattern. RESULTS: When parameters related to the tumor microenvironment were compared with other prognostic parameters, there was a significant relationship between TILs and tumor grade, size, stage, immunohistochemical subgroup and Ki-67 proliferation index. A significant relationship was detected between intratumoral stromal reaction and tumor grade, size, molecular subgroup and the Ki-67 proliferation index (p < 0.05). When stroma and other prognostic parameters were compared, tumors with desmoplastic stroma had higher grades and higher Ki-67 proliferation indexes, and they were observed more frequently in the triple negative molecular subgroup. CONCLUSION: We believe that including parameters related to tumor microenvironment in breast cancer reports, which hold a prognostic and predictive importance, will contribute to patient management. Considering the fact that these can be easily evaluated from routinely used hematoxylin-eosin stained slides, this does not cause additional costs or excessive time loss.

Immunotherapy experience in sinonasal NUT midline carcinoma, case report.

NUT midline carcinoma (NMC) is an aggressive malignant neoplasm arising from midline structures. Although it is classified as a rare disease, the pathological nonspecific appearance as undifferentiated/poorly differentiated carcinoma and the difficulty in making the definitive diagnosis are probably the reasons for the underdiagnosis; the disease is thought to be more prevalent. There is no standard treatment for the disease. The disease shows a poor response to chemotherapy and radiotherapy, and patients' survival is poor. We present a case of sinonasal NMC treated with chemotherapy and immunotherapy in first-line, which is the first in the literature. The patient presented with metastatic disease and received cisplatin-fluorouracil-docetaxel-pembrolizumab treatment. The tumor's PD-L1 expression was 10%, evaluated by tumor proportion score. The response to the therapy was poor, and the patient died of disease progression 5.4 months after the diagnosis. The efficacy of immunotherapy in NMC is not known. More reports are needed to draw conclusions.

Microscopic Growth Pattern of Metastatic Colorectal Carcinomas, Morphological Findings of the Non-Neoplastic Liver, and Their Relationship With Prognosis and Survival.

Introduction. Various clinicopathological, radiological, and molecular parameters are predictive of prognosis in patients with colorectal carcinoma and distant organ metastases continue to have a significant place among them. Recent studies reveal that not only the presence of metastases but also the histopathological growth pattern of the metastatic tumor significantly affects prognosis. This study aimed to investigate the prognostic significance of the histopathological growth patterns of metastatic tumors, the morphological findings in the peritumoral non-neoplastic liver, and its relationship with survival in patients who have metastatic colorectal carcinoma. Materials and Method. Hematoxylin and eosin-stained slides of the tumors were re-examined in terms of histopathological diagnosis, growth pattern, presence and degree of peritumoral lymphocytic infiltration, steatosis, cholestasis, and peritumoral ductular reaction in the non-neoplastic liver. Results. In terms of histopathological growth patterns, 24 (47%) tumors showed replacement, 19 (37%) showed desmoplastic and 8 (16%) showed pushing growth pattern. In terms of total survival, there was a significant difference (P = .011) between desmoplastic and replacement growth patterns, and the survival period was shorter in patients with replacement growth patterns. Conclusion. Recent studies show that histopathological growth patterns in metastatic liver tumors may be a promising prognostic and predictive parameter. It is important to include this parameter in the pathology reports as it does not require additional equipment for evaluation in routine pathology practice, does not bring additional costs, or takes a long time to evaluate. This feature can be evaluated standardly by every pathologist.

Primary Mucinous Cystadenocarcinoma of the Breast: Clinicopathological Analysis of a Case and Difficulties Encountered in a Biopsy.

Background. With <40 case reports published in the English literature, mucinous cystadenocarcinoma of the breast is quite rare compared to its counterparts in the ovary, pancreas, and appendix. The purpose of this case report is to enrich scientific data by sharing the clinicopathological features of this new and extremely rare entity and present possible difficulties encountered in the biopsy materials. Case Report. A 34-year-old female patient presented with the complaint of white discharge from her left nipple lasting 8 months. Physical and radiological examination of the patient revealed a mass in the lower quadrant of the left breast and tru-cut biopsy was performed. The diagnosis of invasive breast carcinoma of no special type was reported. After neoadjuvant chemotherapy, left subcutaneous mastectomy and left sentinel lymph node biopsy were performed. Microscopic evaluation of the mastectomy material revealed a tumor consisting of stratified columnar cells with basally located nuclei and intracytoplasmic mucin, showing papillary structures and tufting toward the lumen. Peripheral myoepithelial cells were not identified with p63 and calponin immunohistochemistry. The diagnosis of mucinous cystadenocarcinoma was given through histomorphological and immunohistochemical evaluations. Conclusion. Clarifying unknown points about this rare malignancy of the breast and understanding the tumor biology is possible through evaluation of case reports. For this purpose, our case of primary mucinous cystadenocarcinoma is presented and its clinicopathological features are briefly discussed.

Liver metastasis of breast carcinoma: An unusual presentation and growth pattern.

Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind.

Early thrombocytopenia predicts longer time­to­treatment discontinuation in trastuzumab emtansine treatment.

Thrombocytopenia is a characteristic adverse event of trastuzumab emtansine (T-DM1), one of the essential treatment options for human epithelial growth factor receptor 2 (HER2)-positive breast cancer. The present study investigated the predictive value of thrombocytopenia for time-to-treatment discontinuation (TTD) in patients receiving T-DM1 for advanced-stage HER2-positive breast cancer. The present observational study enrolled 138 patients who received T-DM1 at six oncology centers from January 2016 to December 2021. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting TTD. The median age of patients was 50 years (range, 26-83). The median number of T-DM1 cycles was 9 (range, 2-58), the overall response rate was 50.0% and the disease control rate was 69.6%. At a median follow-up time of 19.3 months, the median TTD was 9.5 months [95% confidence interval (CI), 7.3-11.7], and the median overall survival was 28.2 months (95% CI, 19.2-37.2). Thrombocytopenia during treatment was observed in 39% of all patients, and 66.7% of these patients experienced early thrombocytopenia (in the first four treatment cycles). Multivariate analysis revealed that the independent factors for TTD were hormone receptor status [hazard ratio (HR), 1.837; 95% CI, 1.249-2.701; P=0.002], Eastern Cooperative Oncology Group performance status score (HR, 3.269; 95% CI, 1.788-5.976; P<0.001) and thrombocytopenia during treatment (HR, 0.297; 95% CI, 0.198-0.446; P<0.001). Patients with early thrombocytopenia had a significantly longer TTD of 17.3 months (95% CI, 11.8-22.8) compared with 7.6 months (95% CI, 5.8-9.4) for patients without early thrombocytopenia (P<0.001). The results of the present study indicated that patients with early thrombocytopenia had improved survival outcomes compared with those without. Thus, maximum benefit from T-DM1 treatment may be achieved by confirming the predictive role of thrombocytopenia in T-DM1 treatment in prospective studies and large-scale cohorts.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Role of Neoadjuvant Chemotherapy in Non-small Cell Lung Cancer in the COVID-19 Pandemic.

Introduction Cancer patients are among the groups at high risk in the COVID-19 pandemic. Here, we aimed to determine the effectiveness of neoadjuvant chemotherapy (NACT) during the pandemic period and examine the prognostic factors in patients with non-small cell lung cancer (NSCLC). Method Patients with stage I-III NSCLC were treated in our hospitals between 2020-2022. Treatment responses were evaluated in patients who underwent NACT. Prognostic factors and the nutritional and inflammatory indexes were investigated. Results Thirty-eight patients received NACT. 57.9% of patients were stage-III. The objective response rate was 57.9%. Pathological complete response was obtained in 10.5% of patients. No prognostic role of inflammatory indices was determined. 21.1% of patients developed a COVID-19 infection. Disease-free survival was 19 months. Survival decreased with large tumor size and presence of metastasis. Conclusion NACT has high response rates. NACT can be used as bridging therapy in suitable patients whose surgery is postponed during the pandemic period.

Platin­based chemotherapy does not improve survival in patients with non­metastatic resected typical carcinoid tumors.

Chemotherapy is controversial in non-metastatic typical carcinoid (TC) tumors. Therefore, it was aimed to evaluate the impact of platin-based chemotherapy on the survival of patients with lung TC. The medical records of patients who underwent surgical resection for non-metastatic TC from 2002 to 2020 at our institution were retrospectively reviewed. Multivariate regression analysis was performed for chemotherapy and prognostic factors in disease-free survival (DFS) in 72 patients. The pathological stages of patients were as follows: 73.6% of the patients were in stage I, 15.3% in stage II and 11.1% in stage III. A total of 5 patients (6.9%) received platin-based chemotherapy and 6 patients (8.3%) had recurrences. The DFS rates at 12, 36 and 60 months were 98.5, 95.1 and 92.5%, respectively. Log-rank testing showed that patients who received chemotherapy and had stage III disease had shorter DFS (P=0.021 for chemotherapy and P<0.001 for stage). However, multivariate analysis revealed that the pathological stage was the only statistically significant factor affecting DFS (P=0.016). Platin-based chemotherapy did not improve DFS, and the eighth edition of TNM (tumor, nodes, metastases) staging did have prognostic value for patients with non-metastatic TC. Although resection has satisfying long-term outcomes, studies on new agents are needed to decrease the recurrence rate, particularly in patients with stage III disease.

Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy.

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.

Why do some patients with stage 1A and 1B endometrial endometrioid carcinoma experience recurrence? A retrospective study in search of prognostic factors.

OBJECTIVES: Endometrial endometrioid carcinoma (EEC) is the most encountered subtype of endometrial cancer (EC). Our study aimed to investigate the factors affecting recurrence in patients with stage 1A and 1B EEC. MATERIAL AND METHODS: Our study included 284 patients diagnosed with the International Federation of Gynecology and Obstetrics stage 1A/1B EEC in our center from 2010 to 2018. The clinicopathological characteristics of the patients were obtained retrospectively from their electronic files. RESULTS: The median age of the patients was 60 years (range 31-89). The median follow-up time of the patients was 63.6 months (range 3.3-185.6). Twenty-two (7.74%) patients relapsed during follow-up. Among the relapsed patients, 59.1% were at stage 1A ECC, and 40.9% were at stage 1B. In our study, the one-, three-, and five-year recurrence-free survival (RFS) rates were 98.9%, 95.4%, and 92.9%, respectively. In the multivariate analysis, grade and tumor size were found to be independent parameters of RFS in all stage 1 EEC patients. Furthermore, the Ki-67 index was found to affect RFS in stage 1A EEC patients, and tumor grade affected RFS in stage 1B EEC patients. In the time-dependent receiver operating characteristic curve analysis, the statistically significant cut-off values were determined for tumor size and Ki-67 index in stage 1 EEC patients. CONCLUSIONS: Stage 1-EEC patients in the higher risk group in terms of tumor size, Ki-67, and grade should be closely monitored for recurrence. Defining the prognostic factors for recurrence in stage 1 EEC patients may lead to changes in follow-up algorithms.

DPYD c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer.

Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects. Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated. Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009). Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.

The impact of Ki-67 index, squamous differentiation, and several clinicopathologic parameters on the recurrence of low and intermediate-risk endometrial cancer.

Endometrial endometrioid carcinoma (EEC) represents approximately 75-80% of endometrial carcinoma cases. Three hundred and thirty-six patients with EEC followed-up in the authors' medical center between 2010 and 2018 were included in our study. Two hundred and seventy-two low and intermediate EEC patients were identified using the European Society for Medical Oncology criteria and confirmed by histopathological examination. Recurrence was reported in 17 of these patients. The study group consisted of patients with relapse. A control group of 51 patients was formed at a ratio of 3:1 according to age, stage, and grade, similar to that in the study group. Of the 17 patients with recurrent disease, 13 patients (76.5%) were Stage 1A, and 4 patients (23.5%) were Stage 1B. No significant difference was found in age, stage, and grade between the case and control groups (p > 0.05). Body mass index, parity, tumor size, lower uterine segment involvement, SqD, and Ki-67 index with p<0.25 in the univariate logistic regression analysis were included in the multivariate analysis. Ki-67 was statistically significant in multivariate analysis (p = 0.018); however, there was no statistical significance in SqD and other parameters. Our data suggest that the Ki-67 index rather than SqD needs to be assessed for recurrence in patients with low- and intermediate-risk EEC.

Efficacy of chemotherapeutics in classic and non-classic Kaposi sarcoma: A single-center retrospective real-world data.

Kaposi sarcoma is a rare disease and there is a gap in the literature about which chemotherapeutics should be applied, especially for the classical type. We aimed to present our institutional data on the demographic characteristics, treatment, and treatment efficacy in 16 Kaposi sarcoma (KS) patients treated with chemotherapy. We retrospectively analyzed the demographic and clinical characteristics, and the chemotherapeutic agents administered to the 16 KS patients diagnosed in our center and treated with chemotherapy, based on the medical records obtained. The median age, gender, type of KS, site of involvement, cytotoxic agents administered, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles of the patients were evaluated. The median age at disease onset was 61.07 years (range, 39.4-85.8 years). Among the patients, 1 had immunosuppression-related KS, 4 had AIDS-related KS, and 11 had classical KS. In the first-line cytotoxic therapy, 7 patients received pegylated-liposomal doxorubicin (PLD), 6 patients received paclitaxel, 2 patients received oral etoposide, and 1 patient received the adriamycin, bleomycin, and vincristine regimen. In the Kaplan-Meier analysis, the PFS was 39.9 months (95% CI, 7.7-72.0). In the first-line setting, a significant difference in terms of PFS was observed between the PLD- and paclitaxel-treated groups (not reached vs. 12.8 months, p = 0.033). The OS was 66.1 months (95% CI, 30.2-102.0). The ORR of the 16 patients was 43.8%, and their DCR was 81.3%. No grade 3 or 4 toxicity was observed. This retrospective study showed that PLD seems better than paclitaxel in terms of PFS and response rates and it has shown to have a good safety profile in KS patients.

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis.

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

Smoking habits are an independent prognostic factor in patients with lung cancer.

OBJECTIVES: The role of tobacco in the pathogenesis of lung cancer (LC) has been clearly established. Based on the epidemiological evidence that smoking may influence LC progression, we investigated the idea that smoking behavior could be associated with overall survival (OS) in this group of patients. METHODS: A total of 351 patients with LC (311 men and 40 women) were reviewed. Smoking status was assessed as tobacco users or non-users. To calculate pack-years of smoking, the average of number of cigarettes smoked per day was divided by 20 to give packs per day, and then multiplied by the total number of years of smoking. OS was the main outcome measure. RESULTS: The mean follow-up was 3.3 ± 1.2 years. Kaplan-Meier plots of OS by use of tobacco revealed significant differences by smoking status (log-rank = 5.44, P < 0.01), indicating a reduced survival rate in tobacco users. The effect on OS of the amount of cigarette smoking was also evident when we subdivided the former and current smokers into ≤7 (mean value) pack-years and >7 pack-years groups (log-rank = 4.27, P < 0.05). After adjusting for all potential confounders, tobacco smoking retained its independent prognostic significance for OS (hazard ratio = 1.53, 95% confidence interval = 1.19-2.17, P = 0.02). CONCLUSIONS: Our data indicate that cigarette smoking is significantly associated with a poor prognosis among patients diagnosed with LC in a dose-dependent manner.

Immunohistochemical expression of CDX2, CK7, HER2 and HER4 in periampullary adenocarcinoma : implications for clinicopathology and patient outcomes.

Background: Periampullary carcinomas originate from the pancreatic head, the ampulla, the distal bile duct, or the duodenum. The expression of CK7 and CDX2 has been used in the classification of periampullary carcinomas. There is prognostic value of human epidermal growth factor receptor (HER) 2 and HER 4, which have been linked to poor prognosis in several types of tumors, such as breast and gastric carcinomas. We aimed to evaluate the expression and prognostic value of CDX2, CK7, HER 2, and HER4 in periampullary adenocarcinoma. Patients and Methods: We retrospectively selected 98 patients who had undergone pancreatoduodenectomy for periampullary adenocarcinoma at our pathology department. The tumor location, pathological subtype, involvement of vessels and lymph nodes, perineural invasion, clinical follow-up, and tumorstage were noted. Immunohistochemistry was performed for CK7, CDX2, HER2, and HER4. Results: CDX2 staining was predictive of perineural invasion. Additionally, there was a significant association between the overexpression of HER2 and HER4 and the presence of perineural invasion. HER4 was significantly positive in patients with the pancreatobiliary subtype compared with patients with the intestinal subtype. Patients with the pancreatobiliary subtype, lymph node involvement, and advanced pT and UICC stages had significantly lower median survival. Conclusion: Our findings suggest that only pancreatobiliary subtype, lymph node involvement and advanced pT and UICC stages were independent predictors of short survival, but the ampulla tumor location predicted a significantly better survival time. The immunohistochemical expression of CDX2, CK7, HER4, and HER2, vessel involvement, and perineural invasion were not associated with the survival of patients with periampullary adenocarcinoma.

Immunohistochemical expression of human epidermal growth factor receptor (HER)-4 and prognosis in patients with metastatic breast cancer.

PURPOSE: The clinical value of HER4 - a cell surface receptor that belongs to the human epidermal growth factor receptor family - for predicting survival outcomes in patients with breast cancer remains controversial. Herein, we sought to investigate the prognostic significance of HER4 immunohistochemical expression with respect to progression-free survival (PFS) and overall survival (OS) in Turkish patients with metastatic breast cancer (MBC). METHODS: MBC patients (N=45; mean age=50.5±12.7 years) were consecutively enrolled between 2000 and 2006 in the Department of Oncology at the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections. The predictive value of HER4 expression was investigated by multivariate analysis after allowance for potential confounders. RESULTS: The mean PFS in the study participants was 11.35 months (range:1-50), whereas the median OS was 22.18 months (range:1-76). The mean PFS in patients with a HER4 immunohistochemical score of 0, 1+, 2+, and 3+ was 11.0 ± 4.8, 11.3 ± 7.7, 11.7 ± 8.1, and 10.4 ± 7.4 months, respectively (p=0.99) . The mean OS in patients with a HER4 score of 0, 1+, 2+, and 3+ was 13.3 ± 6.8, 25.6 ± 10.8, 22.9 ± 10.7, and 13.5 ± 9.9, months, respectively (p=0.44). The results of multivariate Cox regression analysis indicated that the presence of visceral metastases was the only independent prognostic factor for both OS (HR=3.01, 95% CI=1.56-3.99, p <0.01) and PFS (HR=2.91, 95% CI=1.51-3.78, p <0.01). CONCLUSION: HER4 immunohistochemical expression is not an independent predictor of OS and PFS in Turkish MBC patients.