BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure.

INTRODUCTION: BRAFV600E activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAFV600E mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure. MATERIAL AND METHODS: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAFV600E mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised thatBRAFV600E mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012). RESULTS: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed betweenBRAFV600E mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p = 0.002), vascular invasion (p = 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related withBRAFV600E mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%). CONCLUSION: We revealed that BRAFV600E mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAFV600E.

Utilization of Wilms' tumor 1 antigen in a panel for differential diagnosis of ovarian carcinomas.

OBJECTIVE: Ovarian metasteses are often mistaken for primary adenocarcinoma. Studies conducted in recent years have focused on a search for an immunohistochemical marker to aid the differential diagnosis primary and metastatic ovarian carcinoma. Our study objective was to study the usefulness of Wilms tumor 1 (WT 1) antigen in this context. MATERIALS AND METHODS: The study was conducted at the pathology clinic of Lütfi Kirdar Training and Research Hospital. Deparaffinated blocks of 40 epithelial ovarian tumors, 40 colon adenocarcinomas, and 35 cases of omentum metastases were studied. Cytokeratin 7 (CK 7), cytokeratin 20 (CK 20), and WT 1 were applied to all specimens. RESULTS: All ovarian adenocarcinomas were stained with CK 7 (100%). Colorectal adenocarcinomas were stained positive with CK 20 in 87.5% of cases. Primary ovarian adenocarcinomas stained positive with WT 1 in 82.5% of the cases and none of the colorectal adenocarcinomas showed staining with WT 1 (0%). CONCLUSION: WT 1 can be used in conjuction with CK 7 in the differential diagnosis of ovarian carcinomas.

Epithelioid trophoblastic tumor.

OBJECTIVE: To describe a case of epithelioid trophoblastic tumor (ETT) in a postmenopausal woman, which had several peculiar features that differentiate it from previously reported ETTs. CASE REPORT: ETT of the uterus is a rare form of trophoblastic tumor with only 100 cases distinguished until now. Our case differs from the previously reported ones due to its several exceptional features. Our patient had no history of trophoblastic or gynecological disease; is postmenopausal; had endocervical extension from the beginning; recurrences and metastasis at follow up; and had a high Ki-67 index and a normal beta-human chorionic gonadotropin value. CONCLUSION: Because precise differential diagnosis will alter the therapeutic approach and prognosis, it is necessary for treating physicians to be aware of these unusual presentations.

[Evaluation of the Cystic Eccinococcosis Cases Diagnosed in Dr. Lütfi Kirdar Kartal Education and Research Hospital Pathology Laboratory Between 2007 and 2013]. / 2007-2013 Yillari Arasinda Dr. Lütfi Kirdar Kartal Egitim Arastirma Hastanesi Patoloji Laboratuvarinda Tani Alan Kistik Ekinokokkozis Olgularinin Degerlendirilmesi.

OBJECTIVE: The aim of the study was a retrospective evaluation of 299 cases that were histopathologically diagnosed as cystic echinococcosis (CE) in the pathology laboratory of our hospital in a seven years period. METHODS: All specimens sent to the laboratory were examined microscopically following macroscopic and hematoxylin eosin (H-E) staining. 299 cases were reviewed according to age, gender and organ affected by the cyst, more than one specimen of the same organ was evaluated once. RESULTS: Of the 299 cases, 44.5% (133) were male whereas 55.5% (166) of them were female. Additionally, %5 (15) of the cases were between 0-15 ages, %31.8 (95) of them were between 16-30 ages, %29.4 (88) of them were between 31-45 ages, % 24.4 (73) of them were between 46-60 ages and %9.4 (28) of them were older than 61. Cysts were mostly localized in liver, lungs and peritoneal cavity, %71.9 (215), %11.4 (34) and %4.7 (14) respectively. CONCLUSION: Demographic features of our cases were mostly in line with the previous literature. Because of the presence of atypical localized cases, during pathologic evaluation of all surgical cystic specimens, elements of this parasite should be searched and evaluated carefully.

Profile of head and neck cancers in Dr. Lütfi Kirdar Kartal Educational and Research Hospital.

OBJECTIVE: Head and neck cancers account for 17.6% of all malignant neoplasms. Data on the incidence of head and neck cancers and histological subtypes in Turkey are limited. This study aimed to provide an overview of statistics for head and neck cancers. MATERIAL AND METHOD: This retrospective and descriptive study included 1973 cases of in-situ carcinomas, malignant and borderline neoplasia from the head and neck region in a period of 5 years, diagnosed at Dr.Lütfi Kirdar Kartal Education and Research Hospital's Department of Pathology. Demographic data of patients and data from histopathological report were recorded. The topography of all tumours was coded according to the International Classification of Diseases for Oncology, 2nd and 3rd edition and histological and behavioral codes were given according to ICD-O-3. Data was entered and analyzed using Microsoft Excel™, version 2010. RESULTS: Male and female ratio was 1.03 for head and neck cancers. The most common sites for males were described as the ratio in head and neck cancers and all malignant tumours as follows: the skin (non-melanoma) (48.4%-8.2%), the larynx (12.6%-2.3%), the thyroid (11.1%-1.2%), the lips (7.8%-1.3%), and the nasopharynx (3.1%-0.5%). The most common sites for females were as follows: the thyroid (45.3%-8.3%), the skin (non-melanoma) (39.6%-7.3%), the lips (3.6%-0.6%), the nasopharynx (2.2%-0.4%) and the eye (1.7%-0.3%). The male: female ratio was 25.2 for larynx cancers. The most common histological types and rates for males and females were also given. CONCLUSION: This descriptive epidemiological pathology-based cancer incidence study has relative value for describing head and neck cancer incidences in the Istanbul region and shown that pathology report-based descriptive epidemiological studies are still valuable for determination of the regional distribution of cancer incidence out of the active cancer registration regions.

Effects of maternally exposed food coloring additives on laryngeal histology in rats.

Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p<0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p<0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis.

Inducible nitric oxide synthase expression in gastric adenocarcinoma: impact on lymphangiogenesis and lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the most important parameter in the spread of gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an important role in inflammation and carcinogenesis. In this study, the possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated. METHODS: In this study, iNOS expression and D2-40 (lymphatic endothelium-specific marker monoclonal antibody) reactivity were examined immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma and stroma. D2-40-positive lymphatic vessels were used in the determination of lymphatic invasion and intratumoral and peritumoral lymphatic vascular density. RESULTS: iNOS expression was higher in gastric carcinoma tissue compared with non-neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be closely related to lymphangiogenesis and lymphatic metastasis. The density of lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular density were positively correlated with lymph node metastasis. CONCLUSIONS: Our results suggest that iNOS-mediated NO formation plays an important role in gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic metastases. Inhibition of the NO pathway may be an alternative treatment of gastric carcinomas. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388.

Association between human papillomavirus and endometrial adenocarcinoma.

Several studies have suggested a possible role of human papillomavirus (HPV) in the pathogenesis of endometrial carcinoma. The aim of the study was to investigate the presence of HPV DNA in endometrium cancers and nonneoplastic endometrium. Sixty endometrial adenocarcinomas with and without squamous differentiation and the nonneoplastic endometrium tissue of fifty-six of the same patients were analyzed for the presence of family 16 and family 6 HPV DNA by using chromogenic in situ hybridization technique on formalin-fixed and paraffin-embedded archival samples, and the results were confirmed by polymerase chain reaction method. HPV DNA was not detected either in the endometrial adenocarcinoma with or without squamous differentiation, or in the nonneoplastic endometrium tissue. It appears that HPV does not play any role in the pathogenesis of endometrial carcinoma, since endometrium may not to be a suitable host for HPV replication.

Primary cutaneous angiosarcoma on the nose in a patient with multiple nonmelanoma skin cancers.

Cutaneous angiosarcoma is an uncommon, potentially metastatic and highly aggressive vascular tumor that may arise as de novo or be associated with previous radiotherapy. A 70-year-old female with a solitary lesion on the nose was initially diagnosed as actinic keratosis. However, when the recurring lesion at the same region within 6 months was reexcised, the histological diagnosis was definitively established as well-differentiated angiosarcoma. This case was presented in order to increase awareness of this rare malignancy in an uncommon localisation, especially in the light of pathological findings. Moreover, occurrence of cutaneous angiosarcoma within a short period following a previous excision in a patient with a history of multiple nonmelanoma skin cancers was interestingly pointed out.

Prognostic role of sensitive-to-apoptosis gene expression in rectal cancer.

AIM: To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy (CRT) and expression of sensitive-to-apoptosis (SAG), B-cell lymphoma-extra large (Bcl-X(L)) and Bcl-2 homologous antagonist/killer (Bak). METHODS: Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest, namely SAG, Bcl-X(L), Bak and ß-actin, in rectal carcinoma patients who had a follow-up period of 3 years after CRT. Biopsy specimens were excised from the rectal tumor preceding CRT. RESULTS: SAG, Bcl-X(L) and Bak proteins showed significant correlations with each other. In multivariate analysis, patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates: 56% vs 73%, respectively (P = 0.056). On the other hand, there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT. Mean overall survival in the patients with elevated SAG expression was 27.1 mo ± 3.9 mo [95% confidence interval (CI): 19.3-34.9], and in patients with reduced expression, it was 32.1 mo ± 2.5 mo (95% CI: 27.3-36.9). The corresponding values for Bcl-X(L) were 28.0 mo ± 4.1 mo (95% CI: 19.9-36.1) and 31.7 mo ± 2.9 mo (95% CI: 26.0-37.5), and those for Bak were 29.8 mo ± 3.7 mo (95% CI: 22.5-37.2) and 30.6 mo ± 2.4 mo (95% CI: 25.5-35.0), respectively. CONCLUSION: Two-year survival rates significantly correlated with low SAG expression, and SAG may be a candidate gene for good prognosis, independent of therapeutic response of different individuals.

Lymphatic differentiation in classic Kaposi's sarcoma: patterns of D2-40 immunoexpression in the course of tumor progression.

The recent development of lymphatic endothelium-specific immuno-indicators has given rise to research on the histogenesis of Kaposi sarcoma (KS), specifically focusing on its lymphatic root and differentiation. D2-40 is a new lymphatic marker that recognizes podoplanin and is easily applied to formalin-fixed paraffin-embedded human tissues. This study examined D2-40 immunoexpression in 178 classical KS lesions using immunohistochemical methods. D2-40 immunoexpression was also examined in 63 non-KS soft tissue lesions to test the reliability of D2-40 monoclonal antibody in the pathological diagnosis of KS. D2-40 immunoreactivity was detected at all of the KS lesions and in lymphangioma and nonneoplastic lymphatic endothelium. There was no significant relationship between the extent of D2-40 staining and histopathological stage; however, there was a positive correlation between the staining intensity and histopathological stage in KS cases. D2-40 immunoreactivity was detected at all histopathological stages of KS and may be added to the routine immunohistochemical panel used for the differential diagnosis of KS. Widespread D2-40 protein expression is evidence of a lymphatic origin or the differentiation of neoplastic cells in KS, and D2-40 expression increases with tumor progression.

The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast.

Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P≥0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.

Role of human papillomavirus in the development of urothelial carcinoma.

It has been estimated that almost 10% of the worldwide cancer burden is linked to human papillomavirus (HPV) infection. Although the association between HPV and bladder carcinoma has been extensively investigated, data on the role of HPV in bladder carcinogenesis are controversial. The aim of the study was to assess the possible role of human papillomavirus in the development of urothelial bladder carcinomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. Seventy urothelial bladder carcinoma tissues were screened by nested-polymerase chain reaction (PCR) for HPV DNA with a control group of total 18 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia III (CIN III). In the study group, we did not find HPV DNA positivity in any of the urothelial carcinomas. In the control group, 15 out of 18 (83.3%) samples were positive for the HPV DNA. These results indicated that there was no association between HPV infection and urothelial carcinomas.

Investigation of human papillomavirus DNA in colorectal carcinomas and adenomas.

Human papillomavirus (HPV) has been considered to be an etiological agent for anogenital cancers, such as cervical cancer and possibly a subset of cancers of the aerodigestive tract. The aim of the study was to evaluate the presence of human papillomavirus DNA in colorectal carcinomas and adenomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. One hundred and six colorectal carcinomas and 62 adenomas were screened by nested polymerase chain reaction (PCR) for HPV DNA with a control group of 49 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia (CIN). In the study group, we did not find HPV DNA positivity in any of all the colorectal carcinomas and adenomas. In the control group with cervical lesions, 34 out of 49 (69.4%) samples were positive for the HPV DNA. These results indicated that there was no correlation between HPV infection and colorectal carcinomas and adenomas.

The relationship of COX-2 expression with estrogen receptor, progesterone receptor and prognostic parameters in endometrial carcinomas.

AIM: Endometrial cancer (EC), which is the most common gynecologic cancer, develops as a result of disruption of the delicate balance between cell proliferation and cell loss, or apoptosis through activation of oncogenesis, or loss of tumor suppressor genes. Among the biochemical factors proposed to give a more detailed characterization of EC biology, estrogen receptors (ER) and progesterone receptors (PR) play a major role. Most of the studies in the literature have shown increased expression of cyclooxygenase-2 (COX-2) in EC. Recent experiments suggest that COX-2 antagonizes cell apoptosis, increases the invasiveness of malignant cells and promotes angiogenesis. The aim of this study was to investigate the expression of COX-2 in EC, to study its correlation to established menstrual status, grade, myometrial invasion, lymph node status, stage and ER and PR status. MATERIAL & METHODS: The study was performed on 72 ECs. Immunohistochemically was analyzed for ER, PR, and COX-2. RESULTS: COX-2 positivity was found in 91.7% of the cases. In 61 cases (84.7%) there was ER positive staining, and in 59 cases (81.9%) PR positive staining was observed. We have not found a statistically significant relation between COX-2 and prognostic factors, ER and PR. CONCLUSIONS: A high expression rate still suggests a probable relation with endometrial carcinogenesis. If such a relation exists, new therapeutic options might be available in the future.

Expression and prognostic significance of Cox-2 and p-53 in Hodgkin lymphomas: a retrospective study.

BACKGROUND: Cyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2 (cox-2), which is one of the two isoforms, plays a role in tumor progression and carcinogenesis. p53 contributes to apoptosis, DNA renewal and cell cycle. Studies concerning the relationship of cox-2 and p53 expressions and carcinogenesis are available, but the association between cox-2 and p53 in Hodgkin lymphoma (HL) is not exactly known.In our study, we examined the association of cox-2 and p53 expression, with age, stage, histopathological subtype, and survival in HL. We also examined correlation between cox-2 and p53 expression. METHODS: Cox-2 and p53 expressions in Hodgkin-Reed Sternberg cells (HRS) were examined in 54 patients with HL depending on cox-2 expression, stained cases were classified as positive, and unstained cases as negative. Nuclear staining of HRS cells with p53 was evaluated as positive. The classifications of positivity were as follows: negative if<10%; (1+) if 10-25%; (2+) if 25-50%; (3+) if 50-75%, (4+) if >75%. RESULTS: Cox-2 and p53 expressions were found in 49 (80%) and 29 (46%) patients, respectively. There were differences between histological subtypes according to cox-2 expression (p = 0.012). Mixed cellular (MC) and nodular sclerosing (NS) subtypes were seen most of the patients and cox-2 expression was evaluated mostly in the mixed cellular subtype.There were no statistically significant relationships between p53 and the histopathological subtypes; or between p53, cox-2 and the factors including stage, age and survival; or between p53 and cox-2 expression (p > 0.05). CONCLUSION: Considering the significant relationship between the cox-2 expression and the subtypes of HL, cox-2 expression is higher in MC and NS subtypes. However the difference between these two subtypes was not significant. This submission must be advocated by studies with large series.

The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas.

BACKGROUND: Endometrial carcinoma (EC) is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2) gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Immunohistochemical (IHC) analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. RESULTS: We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. CONCLUSIONS: Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

Glioblastoma with primitive neuroectodermal tumor-like features: case report.

Glioblastoma multiforme (GB) is the most aggressive, and the most frequent primary tumor of the brain in adults. Presence of less-differentiated areas which exhibit a small cell morphology and neural immunophenotype is quite uncommon in GBs. Tumor tissue which had been determined in the frontotemporal region of a 61-year-old female patient and evaluated to be consistent with GB radiologically was subjected to total excision. Histopathological examination revealed two different components making up the tumor tissue. Using a morphological and immunophenotypic approach, the predominant component of the tumor was found to bear the properties of classic GB. The other component was composed of undifferentiated areas exhibiting small cell morphology and diffuse neuronal immunophenotype. The case was diagnosed as 'Glioblastoma with primitive neuroectodermal tumor-like component'. The patient who had been subjected to postoperative radiotherapy, showed no sign of recurrence during the follow-up examination performed on the 9th month. The histogenesis and prognostic significance of neuronal differentiation observed in glial tumors are not known yet. Inclusion of this component in pathological reports is important regarding formation of a database for future studies.