Clinicopathological analysis of 38 male patients diagnosed with breast cancer.

BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival. OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes. METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results. RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC. CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach.

The effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues of rats.

OBJECTIVES: Thyroid hormones affect many enzymes, organs, and systems. They also play a role in complex biological events including development and growth. The main objective of this study was to analyze the effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues as well as the treatment of these disorders. METHODS: Thirty-eight Wistar-albino male rats were randomly divided into five groups: 1. Control group (n=6): The rats were sacrificed without any application and liver and heart samples were collected. 2. Hypothyroidism group (n=8): Prophyltiouracil (PTU)-10 mg/kg/day was applied to induce hypothyroidism by intraperitoneal route for two weeks. 3. Hypothyroidism + Thyroxine group (n=8): After one week of PTU application (10 mg/kg/day), a high dose of l-thyroxine (1.5 mg/kg/day) was applied by intraperitoneal route for one week. 4. Hyperthyroidism group (n=8): l-thyroxine (0.3 mg/kg/day) was applied intraperitoneally to induce hyperthyroidism for two weeks. 5. Hyperthyroidism + PTU group (n=8): After one week of high dose l-thyroxine application, PTU (10 mg/kg/day) was applied for one week. RESULTS: Liver and heart tissues were collected to evaluate 8-hydroxy-2 deoxyguanosine (8-OHdG), caspase-8 and caspase-9 levels. Hypothyroidism caused DNA damage in the liver, while hyperthyroidism caused DNA damage in the heart tissue. Hyperthyroidism also led to a significant increase in levels of caspase-8 and caspase-9 in liver tissue. CONCLUSIONS: The results of the study show that DNA damage and caspase levels in the heart and liver are affected differently in experimental hypothyroidism and hyperthyroidism.

Clinical and pathological characteristics of gastrointestinal stromal tumor (GIST) metastatic to bone.

Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years). Morphologically, neoplastic cells were spindle in 67%, epithelioid in 13%, and mixed epithelioid and spindle in 20%. CD117, DOG1, and CD34 were positive in 88, 86, and 85% of the cases, respectively. KIT Exon 11 mutations were the most frequent gene alteration (78%), followed by KIT Exon 13 mutations. Of 17 of the cases with available follow-up information, 7 (41%) patients developed bone metastasis under imatinib therapy. Five patients (29%) died of disease within a mean of 17 months. Bone metastases from GIST are usually found in patients with advanced disease and typically present as lytic masses with occasional soft tissue involvement. We could not identify any KIT or PDGFRA alterations predisposing to bone metastasis.

Comparison of Clinicopathologic Parameters and Survivals Between Epstein-Barr Virus-positive and Her2-positive Gastric Cancers.

Gastric carcinomas are highly mortal neoplasms for which new therapeutic options are being searched. The molecular subtyping of gastric adenocarcinomas was proposed recently, and the relationship between etiopathogenetic types is still under investigation. Here we compared histopathologic, prognostic, and survival differences between Epstein-Barr virus (EBV)-positive and Her2-positive gastric adenocarcinomas. In a retrospective design, we searched the EBV status with Epstein Barr Virus encoded small RNA (EBER) in situ hybridization, and the Her2 status both by immunohistochemistry and by chromogenic in situ hybridization of 106 gastrectomized gastric carcinomas. Histologic and clinical prognostic parameters and survival information were determined, and retrieved from archival tissues and clinical notes. The Her2 positivity rate was 12.3% and the EBV positivity rate was 7.6%. Among EBER-positive cases, Her2 positivity was not detected. Her2 positivity was detected more in intestinal differentiated tumors, whereas EBER positivity was detected in undifferentiated tumors (P=0.003). There was no correlation of Her2 or EBER positivity with the tumor stage. Median survivals of EBER-positive, Her2-positive, and both negative cases were 11.5, 18, and 20.5 months, respectively. The tumor stage and distant metastasis were found to be significant for survival in the multivariate analysis. In our 106 gastrectomized gastric carcinoma cases, EBV-positive and Her2-positive groups were found to be unrelated as proposed in the upcoming classification of gastric carcinomas.

Metastasis of prostate adenocarcinoma to the frontal and ethmoid sinus.

Intracranial metastasis of prostate cancer is rarely seen, and there are few studies in this regard in the literature. Most of these studies in the literature comprise the metastasis of prostate cancer to the sphenoid sinus, and metastasis to the frontal and ethmoid sinus is a much rare entity. Association of visual symptoms, epistaxis, headache, and hematuria may indicate a urologic malignancy in terms of the origin of the primary tumor. This study was aimed to present the prostate cancer case of a 73-year-old patient whose paranasal sinus tomograms revealed the presence of frontal and ethmoid sinus metastasis.

Thyroid FNAC containing hürthle cells and hürthle-like cells: A study of 128 cases.

AIM: It is a diagnostic challenge to differentiate benign and malignant cytology in the presence of Hürthle cells. In our previous study, it was determined that in fine needle aspirations (FNA), the malignancy outcome of the Hürthle cells containing group tend to be papillary thyroid carcinoma (PTC) in a higher percentage. The most common misinterpretation is caused by PTC cells with large cytoplasm-like Hürthle cells. The aim of this study is to predict histologic outcome of the nodules, which have Hürthle cells in FNA according to cytological, clinical features, and BRAFV600E mutation status. MATERIALS AND METHODS: Detailed cytological features of 128 cases were compared with histopathological diagnosis. The analysis of BRAFV600E mutation of the PTC cases were performed by real-time polymerase chain reaction. RESULTS: The neoplastic outcome was increased statistically significantly with younger age (P = 0.020), increase in cellular dyshesion (P = 0.016), presence of nuclear budding (P = 0.046), and granular chromatin (P = 0.003). Nuclear budding (P = 0.014), granular chromatin (P = 0.012), and hypoechoic nodules in ultrasonography (P = 0.011) were significant independent factors for the increase in the malignancy risk. Increased lymphocytes (P= 0.015) and colloid were related to non-neoplastic outcome. According to the surgical outcome, more than half of the malign cases were PTC (74%). BRAFV600E mutation was detected in 27.8% of the PTC cases. CONCLUSION: PTC cases containing Hürthle cell-like cells may lead to diagnostic errors. Nuclear budding and granular chromatin of Hürthle cells are significant, remarkable findings to predict the outcome of neoplasm and malignancy.

Retrospective analysis of oncogenic human papilloma virus and Epstein-Barr virus prevalence in Turkish nasopharyngeal cancer patients.

Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV). Human papilloma virus (HPV) has also been detected in NPC cases. In this retrospective study, we analyze the frequency of EBV and HPV infection in 82 Turkish patients with NPC. A total of 82 were evaluated for EBV and HPV. In situ hybridization (ISH) was performed for EBV. HPV-ISH and P16 immunohistochemistry used to determine the HPV status. Seventy-two of the 82 (87%) NPC patients were EBV-positive. The highest rate of EBV-positivity was found in undifferentiated NPC patients, which accounted for 65 of 68 (95.6%) undifferentiated cases. One of the 82 NPC patients whose tumor was non-keratinizing differentiated, contained HPV. Our data shows that EBV is closely associated with NPC in Turkey. We found lower rates of HPV-positivity in NPC patients than in North American populations. In addition, both EBV and HPV-negativity were more associated with decreased survival than EBV-positive cases.

Skin punch biopsy sectioning: before or after tissue processing?

BACKGROUND: We intended to study whether there is a meaningful difference in microscopic examination between dividing a biopsy section into two equal parts before tissue processing (first method) or after (second method). METHODS: A total of 400 cases were included in the study. Punch biopsies (PB) were cut into two pieces using the first method in 200 cases and just before paraffin embedding in another 200 cases using the second method. We microscopically evaluated the epidermal mesh view, the presence of a cross-cut hair follicle and bow shape because of epidermal angling, the presence of two pieces on the slide and if there was a difference of >2 mm between the parts, and the number of new sections and new slides. RESULTS: Cross-cut hair follicle (p = 0.018), epidermal mesh view (p = 0.036), difference of >2 mm between the parts (p = 0.008), the number of new sections (p < 0.001) and new slides (p < 0.001) were considerably higher when the first method was used compared with the second method. The presence of two pieces was less (p < 0.001) when using the first method. CONCLUSIONS: We noted a meaningful difference in the quality of microscopic evaluation between the first and second methods. Better sections were obtained with the second method. In addition, the decrease in the number of new slides will reduce workload, archival work and cost.

The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial-mesenchymal transition in breast cancer.

Tumor cells develop drug resistance which leads to recurrence and distant metastasis. MicroRNAs are key regulators of tumor pathogenesis; however, little is known whether they can sensitize cells and block metastasis simultaneously. Here, we report miR-644a as a novel inhibitor of both cell survival and EMT whereby acting as pleiotropic therapy-sensitizer in breast cancer. We showed that both miR-644a expression and its gene signature are associated with tumor progression and distant metastasis-free survival. Mechanistically, miR-644a directly targets the transcriptional co-repressor C-Terminal Binding Protein 1 (CTBP1) whose knock-outs by the CRISPR-Cas9 system inhibit tumor growth, metastasis, and drug resistance, mimicking the phenotypes induced by miR-644a. Furthermore, downregulation of CTBP1 by miR-644a upregulates wild type- or mutant-p53 which acts as a 'molecular switch' between G1-arrest and apoptosis by inducing cyclin-dependent kinase inhibitor 1 (p21, CDKN1A, CIP1) or pro-apoptotic phorbol-12-myristate-13-acetate-induced protein 1 (Noxa, PMAIP1), respectively. Interestingly, an increase in mutant-p53 by either overexpression of miR-644a or downregulation of CTBP1 was enough to shift this balance in favor of apoptosis through upregulation of Noxa. Notably, p53-mutant patients, but not p53-wild type ones, with high CTBP1 have a shorter survival suggesting that CTBP1 could be a potential prognostic factor for breast cancer patients with p53 mutations. Overall, re-activation of the miR-644a/CTBP1/p53 axis may represent a new strategy for overcoming both therapy resistance and metastasis.

The correlation of sodium iodide symporter and BRAF(V600E) mutation in classical variant papillary thyroid carcinoma.

BRAF(V600E) mutation was analyzed by real-time polymerase chain reaction in 96 consecutive cases with classical variant papillary thyroid cancer, and immunohistochemical staining of Na+/I- symporter (NIS) protein was evaluated. Localization (intracellular or membranous), density, and the intensity of cytoplasmic staining were characterized semiquantitatively. Extrathyroidal invasion, surgical margin positivity, and lymph node metastasis were compared with BRAF(V600E) mutation and NIS expression. Eighty-eight patients who had at least 24-month follow-up were also included in survival analysis. BRAF(V600E) mutation was determined in 78.1% (75/96) and functional NIS activity in 74% (71/96) of the cases. There were statistically significant differences in mean ages between BRAF(V600E) mutation-positive (48.6) and BRAF(V600E) mutation-negative cases (37.3; Levene test, P=.419; Student t test, P=.001). The surgical margin positivity (46.7%) and extrathyroidal extension percentage (54.7%) in the BRAF(V600E) mutation-positive group were higher than the negative (28.6% and 33.3%, respectively) group, without statistical significance (P=.138 and P=.084, respectively). Functional NIS activity was higher in BRAF(V600E) mutation-positive cases (78.1%) than mutation-negative ones (57.1%; P=.047). The possibility of moderate and intense cytoplasmic staining in BRAF(V600E) mutation-positive cases (72%) was 6.3 times higher than the possibility of weak staining (28%) in the mutation-positive cases (95% confidence interval, 2.2-18.8; P=.001). Functional NIS expression is higher in patients with classical variant papillary thyroid cancer with BRAF(V600E) mutation. However, the clinical features were not found to be associated with NIS expression. There may be different mechanisms determining the outcome of therapy.

The role of collecting bladder wash fluid before biopsy procedure to help the cytological diagnosis of residual tumor.

BACKGROUND: Urinary cytology has low sensitivity and specificity in urinary neoplasm. AIM: We planned to assess whether the examination of bladder washing before biopsy (WBB) plays a role in better cytologic diagnosis of bladder wash fluid collected after biopsy procedure (WAB) in papillary urothelial neoplasms. MATERIALS AND METHODS: We included 36 patients with papillary lesion of bladder. Prior to the biopsy, the bladder is washed and fluid is collected for cytology; later transurethral resection (TUR) is performed, then bladders are washed again and the fluid is separately collected for cytology. Both fluids were centrifuged and stained with May-Grünwald Giemsa (MGG). First the WAB slides were evaluated and diagnosed. After evaluation of the WBB slides, the WAB slides were rediagnosed. Presence of cellularity, papillary structure, fusiform cells, background bleeding, and cytolysis in WBB and WAB were evaluated separately. RESULTS: We determined that 31 WBB samples were hypercellular, and 12 of them remained as hypercellular in WAB. Papillary structures were observed in 20 WBB samples; and in one WAB cytology. In 29 cases where no fusiform cells are identified in WBB, 22 showed fusiform cells in WAB. Cytolysis in WABs was noted in 15 cases whose WBBs did not show cytolysis. The decrease in cellularity, papillary structure (P < 0.001, both), cytolysis (P = 0.008), and fusiform cells (P < 0.001) were statistically significant. After seeing the WBB slides, we reevaluated the WAB slides. Out of the eight out of 36 (22.2%) samples diagnosed with degeneration previously, five (62.5%) samples were rediagnosed as benign, two (25%) as cytologic atypia which favor reactive, and one (12.5%) as malignant. CONCLUSION: Due to the better quality, initial evaluation of WBB may help more effective diagnoses of WAB slides.

The diagnostic accuracy of ultrasound-guided fine-needle aspiration biopsy for thyroid nodules three centimeters or larger in size.

BACKGROUND AND PURPOSE: Whether under ultrasonography (US) guidance or not, fine-needle aspiration biopsy (FNAB) has some limitations, particularly in larger nodules. In this study, we aimed to evaluate the diagnostic value of US-guided fine-needle aspiration biopsy (US-FNAB) in thyroid nodules equal to or larger than 3 cm. MATERIALS AND METHODS: Data of 267 patients operated for nodular goiter in the period of January 2006 and March 2012 were reviewed retrospectively. The study group (40 males, 104 females; mean age 42.3 ± 12.3, between 17 and 71) consisted of patients with nodules with a diameter of 3 cm or larger. Patients with nodules less than 3 cm in diameter were considered as the control group (27 males, 96 females; mean age 44.4 ± 11.9, between 18 and 71). RESULTS: For nodules smaller than 3 cm, US-FNAB had an accuracy rate of 60% and a false negativity rate of 21.9%. In nodules equal to or larger than 3 cm, the accuracy rate of US-FNAB was 80%, with a false negativity rate of 6.7%. Malignancy was observed in 16% of the study group and 42.3% of the control group. CONCLUSION: This study showed that increased nodule diameter is not associated with limitations in the diagnostic value of US-FNAB. We also found that the malignancy rate was smaller for larger nodules. This finding reflects the importance of accurate and rational diagnostic work-up and clinical management for detecting malignancy and surgical decision-making.

Histopathological findings obtained from reduction mammoplasty specimens.

BACKGROUND/AIM: Reduction mammoplasty is a common surgical procedure. We report the incidence of nonproliferative and proliferative breast lesions in breast reduction specimens from a single institution over a 6-year period. MATERIALS AND METHODS: The histopathology reports of all patients were analyzed. The clinical and histopathological findings of the patients were recorded. RESULTS: Between 2004 and 2010, 106 patients underwent breast reduction. Fifty-six patients (52.8%) had proliferative breast lesions, 84 patients (79.2%) had nonproliferative lesions, 8 patients (7.5%) had columnar cell lesions without atypia, 61 patients (57.5%) had columnar cell lesions with atypia, 5 patients (4.7%) had atypical ductal hyperplasia, and 6 patients (5.6%) had lobular carcinoma in situ. No invasive breast cancer was identified. CONCLUSION: In Turkey, there is limited evidence regarding the role of histopathological analysis in reduction mammoplasty. Moreover, none of the previous studies determined columnar cell lesion rates in reduction mammoplasty patients. The detection of significantly elevated columnar cell lesions, with or without atypia, especially in patients under the age of 40, increases the importance of screening tests, especially in Turkey, which has a high incidence of breast cancer in early ages, and addresses the need to starting screening tests early in these patients.

Evaluation of cytopathological findings in thyroid nodules with macrocalcification: macrocalcification is not innocent as it seems / Avaliação dos achados citopatológicos em nódulos tiroidianos com macrocalcificações: elas não são tão inocentes como parecem

Objective Microcalcification is strongly correlated with papillary thyroid cancer. It is not clear whether macrocalcification is associated with malignancy. In this study, we aimed to assess the result of fine needle aspiration biopsies (FNAB) of thyroid nodules with macrocalcifications. Subjects and methods We retrospectively evaluated 269 patients (907 nodules). Macrocalcifications were classified as eggshell and parenchymal macrocalcification. FNAB results were divided into four groups: benign, malignant, suspicious for malignancy, and non-diagnostic. Results There were 79.9% female and 20.1% male and mean age was 56.9 years. Macrocalcification was detected in 46.3% nodules and 53.7% nodules had no macrocalcification. Parenchymal and eggshell macrocalcification were observed in 40.5% and 5.8% nodules, respectively. Cytologically, malignant and suspicious for malignancy rates were higher in nodules with macrocalcification compared to nodules without macrocalcification (p = 0.004 and p = 0.003, respectively). Benign and non-diagnostic cytology results were similar in two groups (p > 0.05). Nodules with eggshell calcification had higher rate of suspicious for malignancy and nodules with parenchymal macrocalcification had higher rates of malignant and suspicious for malignancy compared to those without macrocalcification (p = 0.01, p = 0.003 and p = 0.007, respectively). Conclusions Our findings suggest that macrocalcifications are not always benign and are not associated with increased nondiagnostic FNAB results. Macrocalcification, particularly the parenchymal type should be taken into consideration. Arq Bras ...

Objetivo A microcalcificação está fortemente correlacionada com o câncer papilar de tiroide. Não está claro se a macrocalcificação também está associada com malignidade. Neste estudo, nosso objetivo foi avaliar o resultado da biópsia de aspiração por agulha fina (FNAB) de nódulos tiroidianos com macrocalcificações. Sujeitos e métodos Avaliamos retrospectivamente 269 pacientes (907 nódulos). As macrocalcificações foram classificadas como periféricas (casca de ovo) ou parenquimatosas (interna). Os resultados da FNAB foram divididos em quatro grupos citológicos: benignos, com malignidade, suspeita de malignidade e não diagnósticos. Resultados Das amostras, 79,9% foram coletadas de mulheres e 20,1% de homens, e a idade média foi de 56,9 anos. A macrocalcificação foi detectada em 46,3% dos nódulos, e em 53,7% dos nódulos não havia macrocalcificação. A macrocalcificação parenquimatosa e periférica foi observada em 40,5% e 5,8% dos nódulos, respectivamente. Em termos citológicos, a malignidade e suspeita de malignidade foram mais comuns em nódulos com macrocalcificação em comparação com nódulos sem macrocalcificação (p = 0,004 e p = 0,003, respectivamente). Resultados benignos e não diagnósticos da citologia foram similares em ambos os grupos (p > 0,05). Os nódulos com calcificações periféricas apresentaram uma taxa maior de suspeita de malignidade e os nódulos com macrocalcificação parenquimatosa apresentaram ...

Urinary neopterin levels in patients with thyroid cancer.

Increased urinary neopterin concentrations have been described in many cancers. We aimed to evaluate the urinary neopterin levels in thyroid cancer. Sixty-nine patients with thyroid cancer, 76 patients with benign thyroid pathology and 33 healthy subjects were evaluated. First morning urine samples were collected from the patients and normal subjects for neopterin and creatinine measurement and stored at -80 °C until analysed. Neopterin levels were 149.3 (15.2-1,602.2) µmol/mol creatinine in the malignant group, 32 (5.2-275.6) µmol/mol creatinine in the benign group and 9.2 (2.7-78.7) µmol/mol creatinine in normal subjects (p ≤ 0.001). Urinary neopterin levels were significantly higher in patients with thyroid cancer than patients with benign thyroid pathologies and normal subjects. Also the patients with benign thyroid pathologies had a higher urinary neopterin level than the normal subjects. Malignant group was divided to two groups; patients with/without chronic thyroiditis (confirmed histologically). There were 22 (31.9 %) patients with and 47 (68.1 %) patients without chronic thyroiditis. Urinary levels of neopterin didn't differ in both groups (168.6 (21.3-716.8) µmol/mol creatinine and 135.3 (15.2-1,602.2) µmol/mol creatinine respectively; p = 0.381). Urinary neopterin levels are high in thyroid cancer patients independently from the presence of chronic thyroiditis.

microRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers.

Triple Negative Breast Cancers (TNBC) is a heterogeneous disease at the molecular and clinical level with poor outcome. Molecular subclassification of TNBCs is essential for optimal use of current therapies and for development of new drugs. microRNAs (miRNA) are widely recognized as key players in cancer progression and drug resistance; investigation of their involvement in a TNBC cohort may reveal biomarkers for diagnosis and prognosis of TNBC. Here we stratified a large TNBC cohort into Core Basal (CB, EGFR and/or CK5, 6 positive) and five negative (5NP) if all markers are negative. We determined the complete miRNA expression profile and found a subset of miRNAs specifically deregulated in the two subclasses.We identified a 4-miRNA signature given by miR-155, miR-493, miR-30e and miR-27a expression levels, that allowed subdivision of TNBCs not only into CB and 5NP subgroups (sensitivity 0.75 and specificity 0.56; AUC=0.74) but also into high risk and low risk groups. We tested the diagnostic and prognostic performances of both the 5 IHC marker panel and the 4-miRNA expression signatures, which clearly identify worse outcome patients in the treated and untreated subcohorts. Both signatures have diagnostic and prognostic value, predicting outcomes of patient treatment with the two most commonly used chemotherapy regimens in TNBC: anthracycline or anthracycline plus taxanes. Further investigations of the patients' overall survival treated with these regimens show that regardless of IHC group subdivision, taxanes addition did not benefit patients, possibly due to miRNA driven taxanes resistance. TNBC subclassification based on the 5 IHC markers and on the miR-155, miR-493, miR-30e, miR-27a expression levels are powerful diagnostic tools. Treatment choice and new drug development should consider this new subtyping and miRNA expression signature in planning low toxicity, maximum efficacy therapies.

Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options.

Triple negative breast cancers are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapeutics. Androgen receptor has been associated with triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined androgen receptor protein expression by immunohistochemical analysis in 678 breast cancers, including 396 triple negative cancers. Fifty matched lymph node metastases were also examined. Association of expression status with clinical (race, survival) and pathological (basal, non-basal subtype, stage, grade) features was also evaluated. In 160 triple negative breast cancers, mRNA microarray expression profiling was performed, and differences according to androgen receptor status were analyzed. In triple negative cancers the percentage of androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases), especially in African American women (16.7% vs 25.5% of cancers of white women). No significant difference in androgen receptor expression was observed in primary tumors vs matched metastatic lesions. Positive androgen receptor immunoreactivity was inversely correlated with tumor grade (p<0.01) and associated with better overall patient survival (p = 0.032) in the non-basal triple negative cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6) showed significant deregulation in association with androgen receptor status; eg CDK6, a novel therapeutic target in triple negative cancers, showed significantly higher expression level in androgen receptor negative cases (p<0.01). These findings confirm the prognostic impact of androgen receptor expression in non-basal triple negative breast cancers, and suggest targeting of new androgen receptor-related molecular pathways in patients with these cancers.

Malignancy rate of thyroid nodules defined as follicular lesion of undetermined significance and atypia of undetermined significance in thyroid cytopathology and its relation with ultrasonographic features.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as the most accurate, safe, and cost-effective method for evaluation of thyroid nodules. The most challenging category in FNAB is atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS). The Bethesda system (BS) recommends repeat FNAB in that category due to its low risk of malignancy. In our study, we aimed to investigate the malignancy rate of thyroid nodules of AUS and FLUS and whether there were different malignancy rates among the different patterns in this category, and to evaluate the presence of biochemical, clinical, and echographic features possibly predictive of malignancy related to AUS and FLUS. Data of 268 patients operated for AUS and FLUS cytology were screened retrospectively. Ultrasonographic features and thyroid function tests, thyroid antibodies, scintigraphy, and histopathological results were evaluated. Of the 268 patients' results, 276 nodules are evaluated. Malignancy rates were 24.3 % in the AUS group, 19.8 % in the FLUS group, and 22.8 % in both groups. In the evaluation of all nodules, the predictive features of malignancy are hypoechogenicity and peripheral vascularization of the nodule. We determined that the malignancy rates in these nodules are higher than that in the literature rate. This high ratio may be due to the fact that we studied only patients who underwent surgery. The ultrasonographic features alone may be insufficient to predict the malignancy; therefore, all the clinical and ultrasonographic features must be considered in the evaluation of the thyroid nodules. In addition, we think that the recommended management of repeat FNAB in these groups must be reconsidered with the clinical and ultrasonographic features.

Molecular features of follicular variant papillary carcinoma of thyroid: comparison of areas with or without classical nuclear features.

We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARÉ£ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARÉ£ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARÉ£ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop.

"The diagnostic accuracy of thyroid nodule fine-needle aspiration cytology following thyroid surgery: a case-control study".

Thyroid surgery may cause regional scarring and some degree of fibrotic process which may extend into the perithyroidal soft tissues. This may result in problems when collecting thyroid fine-needle aspiration biopsy (FNAB) samples and evaluating the cellular abnormalities. This study aimed to determine if a history of thyroid surgery is a risk factor for nondiagnostic (ND) FNAB results. Patients with ≥1 discrete nodular lesion of the thyroid who underwent FNAB were included. The patients with a history of thyroid surgery constituted group 1, and the others constituted group 2. The factors which may influence FNAB results, including age, gender, presence of Hashimoto's thyroiditis, and ultrasound characteristics, were also evaluated. Group 1 included 123 patients with 200 nodules, and group 2 included 132 patients with 200 nodules. The two groups were similar with respect to demographic characteristics of the patients and ultrasonographic features of the nodules including diameter, content (cystic or solid), echogenicity, margin, and calcifications (P > 0.05). In all, 176 (44 %) of the participants had ND FNAB results. The median time interval between thyroid surgery and FNAB was 15 years [range, 1-45 years; interquartile range (IQR) 13 years]. Significantly more nodules in group 1 had ND FNAB results than in group 2 [98 (49 %) vs 78 (39 %), respectively, P = 0.028]. Multivariate analysis revealed that history of thyroid surgery was independently associated with ND FNAB [odds ratio (OR) 1.55, 95 % confidence interval (CI) 1-2.33, P = 0.033]. A history of thyroid surgery increases the risk of initial ND FNAB.