Clinicopathologic significance of human epidermal growth factor receptor 2 expression and gene amplification in gastric carcinoma.

Aim: This study is aimed at determining the human epidermal growth factor receptor-2 (HER-2) gene status in gastric cancers using immunohistochemistry (IHC) and silver DNA in situ hybridization (SISH) technique and investigating the relationship between HER-2 status and clinicopathological variables. Materials and Methods: We examined 104 gastric carcinoma cases with gastrectomy specimens. The age, sex, histopathological tumor type, tumor differentiation, tumor localization, tumor size, invasion depth, lymph node metastasis status, HER-2 IHC evaluation results, and SISH evaluation results of the cases were recorded. Results: In the present study, the SISH-confirmed HER-2 positivity rate (SISH amplification) is 14.4%. A statistically significant relationship was found between HER-2 status and tumor invasion depth (P = 0.03). It was observed that as the depth of invasion increased, HER-2 positivity decreased. No statistically significant relationship was found between HER-2 status and sex, age, tumor size, differentiation, histopathological classification, lymph node metastasis, and tumor localization (P > 0.05). The rate of HER-2 2+ cases was found to be high. Conclusion: HER-2 status is negatively correlated with the depth of invasion in gastric cancers, and HER-2 positivity increases as the depth of invasion decreases. HER-2 may be early molecular evidence in oncogenesis. Immunohistochemically, HER-2 2+ cases should be confirmed by the in situ hybridization (ISH) technique.

A single centre experience in Turkey for comparison between core needle biopsy and surgical specimen evaluation results for HER2, SISH, estrogen receptors and progesterone receptors in breast cancer patients.

Background: Breast carcinoma diagnosis can be made with core-needle biopsy (CNB), but there are controversies regarding the evaluation of hormone receptor (HR) status in needle biopsy specimens. When preoperative neoadjuvant therapy is required in breast cancer cases, the CNB specimen should be evaluated to decide on the treatment. Objectives: In this study, we aimed to compare the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and silver in situ hybridization (SISH) results of the CNB specimens and surgical specimens (SS) of our breast carcinoma cases. Materials and Methods: This retrospective study included cases diagnosed with breast cancer in our center for approximately 1 year between 2017 and 2018. About 97 cases with both CNB specimens and SS were included in the study. Data such as the ER, PR, HER2, and SISH evaluation results in CNB and SS, age distribution and histopathological type, metastatic lymph nodes, lymphovascular invasion, tumor size, and grade of the tumor were recorded. The data were analyzed using SPSS 22.0 (Statistical Package for the Social Sciences, Armonk, NY, USA) software. Results: All of the cases were female and 70.1% of them were aged over 45. About 27.8% of the cases were aged 31-45 years, and 2.1% were aged under 30. When evaluated according to the histopathological type of the tumor, 71.1% of cases were invasive ductal carcinoma (IDC), 8.2% were invasive lobular carcinoma (ILC), 6.2% were IDC + ILC, 11.3% were another carcinoma, and 3.1% were in situ carcinoma. 12.4% of the cases were Grade I, 43.3% were Grade II, and 20.6% were Grade III. 43.3% of our cases' tumor size were ≤2 cm and 56.7% >2 cm. 50 (51.5%) of these cases had no lymph node metastasis. It was found out that 36 (37.1%) of the cases had 1-4 metastatic lymph nodes and 11 (11.3%) of them had 5 and more metastatic lymph nodes. It was found out that 44 (45.4.%) of the cases had no lymphovascular invasion and 53 (54.6%) of them had a lymphovascular invasion. When HR statuses in CNB and SS were compared, ER was found to have a sensitivity of 96.1% and a specificity of 100%. PR was found to have a sensitivity of 94.2% and a specificity of 66.7%. HER2 was found to have a sensitivity of 100% and a specificity of 73.4%. Conclusion: ER evaluation results are reliable in deciding on needle biopsy material. PR may show the heterogeneous distribution in HER2 tumor. Thus, if PR and HER2 results in needle biopsy material are negative, assessments should be repeated in SS.

The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.

AIM: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features. MATERIALS AND METHODS: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded. RESULTS AND CONCLUSIONS: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.

Incidental papillary thyroid microcarcinomas in thyroidectomy specimens: A single-center experience from Turkey.

BACKGROUND: Papillary thyroid microcarcinoma (PTM) is a relatively common entity in the general population. PTM is often asymptomatic and is detected incidentally during the histopathological examination of thyroidectomy specimens from operations because of benign thyroid disease. AIMS: The aims of the study are to determine the incidence of incidental papillary thyroid microcarcinomas (IPTMs) in our center, to examine the clinicopathologic characteristics of these tumors, and to present our experiences. MATERIALS AND METHODS: This study includes 827 patients who underwent thyroidectomy operation in our center between January 2013 and June 2017 and were examined histopathologically in the Pathology Clinic. Patients' demographic characteristics, preoperative diagnoses, operative procedure, histopathological findings, and postoperative prognostic indexes are presented. RESULTS AND CONCLUSION: Of the 827 patients, 138 (16.6%) were diagnosed with a malignancy. Of these, 124 were papillary carcinoma, 5 were follicular carcinoma, 4 were lymphoma, 2 were medullary carcinoma, 2 were anaplastic carcinoma, and 1 was poorly differentiated carcinoma. The IPTM incidence rate was 8.01%; the multifocality and bilaterality rates were 23.3% and 13.3%, respectively. In 98.3% of IPTM cases, total thyroidectomies were performed, and in 1.7% of cases, subtotal thyroidectomy was performed followed by complementary thyroidectomy. No relapse or metastasis was detected in any of these cases. A careful histopathological examination of the thyroidectomy specimen is essential because IPTM is frequently skipped in fine needle aspiration cytology. We consider it best to perform total thyroidectomies because bilaterality and multifocality rates are high in IPTM. Long-term life expectancy in these tumors is quite good.

Neuroendocrine tumors detected in appendectomy specimens: ten-year single-center experience

Background/aim: The aim of this study was to investigate neuroendocrine tumors (NETs) detected in appendectomy specimens and the incidence and clinicopathologic characteristics of these tumors in our center. Materials and methods: A total of 13,863 patients were evaluated retrospectively. All underwent appendectomy operation in the Kayseri Training and Research Hospital and had a histopathological examination at the Pathology Clinic between January 2007 and March 2017. Age, sex, preoperative clinical findings, operation procedure, and histopathological examination results of the cases reported to be NET are presented. Results: NET was detected in 29 cases (0.2%) in the histopathological examination of 13,863 appendectomy specimens. Of these, 26 were classical carcinoid tumors and 3 were goblet cell carcinoid tumors (GCCTs). For the NET cases, the mean age was 37 years and the male to female ratio was 1.07. Only 68.9% of the patients underwent an appendectomy, and 31% of the patients underwent a secondary right hemicolectomy. Recurrences were not detected in any of the cases. In the present study, coincidence was determined in all of the cases with NET in the appendix. Conclusion: Contrary to many studies, both NETs of the appendix and GCCT cases were slightly higher among males and advanced age groups in this study. The long-term life expectancy in cases of classical carcinoid tumors of the appendix is quite good.

Invasive papillary breast carcinoma, solid variant with neuroendocrine differentiation.

Invasive papillary carcinoma, solid variant is a rarely observed breast tumor. It is encountered in patients of advanced ages and has a good prognosis. After the physical examination, mammography, and ultrasonography examinations, modified radical mastectomy were applied to the 72-year-old patient, who came to our hospital complaining of a mass in the left breast. During the macroscopic analysis, a well-limited, necrotic, and bleeding tumor with a diameter of 7 cm was found in the left breast, covering almost the whole area. The case was diagnosed as invasive papillary carcinoma, solid variant with neuroendocrine differentiation, which has been reported in the literature as a result of the histopathological and immunohistochemical analysis.

Prognostic Value of Cancer Stem Cell Markers CD44 and ALDH1/2 in Gastric Cancer Cases

Purpose: To determine expression levels of CD44 and ALDH1/2, known cancer stem cell (CSC) markers, in stomach adenocarcinomas and assess relationships with clinicopathologic parameters and prognosis. Methods: Eighty patients diagnosed with gastric cancer between the years 2011-2015 were included in this study of clinicopathologic characteristics, postoperative prognostic indexes and stem cell marker CD44 and ALDH1/2 expression in paraffin-embedded tumour sections analyzed immunohistochemically. Clinicopathologic parameters were evaluated using the chi-square test and t-test. Survival analyses were conducted using Kaplan-Meier statistics. Results: We observed positive CD44 and ALDH1/2 staining in 45.0 % and 67.5% of tumour tissues, respectively, but not in normal gastric mucosa. Recurrence-free survival (RFS) was found to be shorter in cases with high levels of CD44 expression (p=0.004). Similarly, short RFS was observed in patients with high levels of CD44 and ALDH1/2 co-expression (p=0.004). Furthermore, tumour invasion depth was found to correlate with high CD44 and ALDH1/2 co-expression (p=0.028). Conclusion: The cancer stem cell markers CD44 and ALDH1/2 may indicate poor patient prognosis and play a role in tumour development and invasion.

Goblet cell carcinoid of the appendix and mixed adenoneuroendocrine carcinoma: Report of three cases.

Neuroendocrine neoplasms are the most common epithelial tumors among appendix tumors. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two categories: Classic carcinoid tumors and goblet cell carcinoid tumors (GCCT). They are known to progress more aggressively than classic (neuro) endocrine tumors. In this study, three cases with acute appendicitis symptoms are presented, including their clinical and histopathological findings. Microscopic examination detected GCCT in two cases and mixed adenoneuroendocrine carcinoma in one case, in addition to acute appendicitis.

Protective role of misoprostol in prevention of gentamicin ototoxicity.

OBJECTIVES: To demonstrate potential protective effect of misoprostol on cochlear toxicity caused by gentamicin with electrophysiological tests and histopathological studies. MATERIALS AND METHODS: The study included 80 ears of 40 rats with normal hearing threshold and DPOAE value in both ears. Animals were assigned into 4 groups. The rats were randomized into 4 groups. Group I (n = 10): Gentamicin, Group II (n = 10): Gentamicin plus misoprostol, Group III (n = 10): Saline; Group IV (n = 10): Misoprostol. All drugs used in the study were given once daily for 15 days. DPOAE and ABR measurements were repeated after drug administration. Subsequently, the rats' cochleae were examined histopathologically. Baseline DPOAE and ABR values were compared to those obtained after drug exposure and cochlear toxicity was evaluated in electrophysiological manner. RESULTS: When At baseline, there were no significant differences in DPOAE responses at frequencies of 1001, 1501, 2002, 3003, 4004, 6006 and 7996 Hz among groups. However In DPOAE test, statistically significant difference was observed between the pre-study basal values and post-study results in groups other than gentamicin + misoprostol group. Additionally, It was found that there was a significant difference in DPOAE response at frequency of 4004 Hz obtained at baseline and after drug exposure according to measurements of epithelial vacuolization in stria vascularis. While ABR threshold values were compared at baseline, there were no significant difference in ABR threshold values of left and right ear between groups. Histopathologically it was also found that there were significant differences measurements of epithelial vacuolization in stria vascularis and inflammation among groups (p < 0.05). CONCLUSION: By these results, misoprostol, a potent antioxidant, has protective effect against cochlear damage, and that may be a safe alternative.

Immunohistochemical expression profiles of BRAF (V600E/VE1) in serrated colon polyps in Turkish population.

BACKGROUND AND AIM: Colon carcinoma, as one of the most common cancers, has been investigated for genetic alterations. Besides well-known adenoma-carcinoma sequence, it is recently found that BRAF mutation had an important role particularly in early stages of adenocarcinomas with serrated features. There are no any studies concerning immunohistochemical expression status of BRAF V600E (VE1) antibody in serrated polyps in the Turkish population. The objective of this study is to observe the immunohistochemical staining of BRAF V600E (VE1) antibody in colon polyps in the Turkish population and investigate the frequency of presence of mutated BRAF proteins indicating malignant potential. MATERIALS AND METHODS: 59 cases of serrated polyps (27 cases of hyperplastic polyps, 18 cases of sessile serrated adenoma/polyps and 14 cases of traditional serrated adenomas) and 10 tubular adenomas, and 10 samples of normal colonic mucosa were immunohistochemically evaluated for the presence of BRAF V600E mutated proteins with the VE1 antibody. Results were statistically compared. RESULTS: All SSA/Ps; 92.8% of TSAs; 37% of HPs were stained positively. Of the 27 hyperplastic polyps, all GCHPs were negative but 10 of 12 MVHPs (83.3%) were weakly positive with the VE1 antibody. Cases in control groups and tubular adenomas didn't show any cytoplasmic staining. CONCLUSION: Serrated adenoma/polyps have been gaining much more importance because of their malignant potential. Their frequency is also relatively high in the Turkish population and they should be carefully handled. Detection of BRAF V600E status can be easily achieved immunohistochemically by VE1 antibody. It is easily applicable and reproducible method and it might be helpful in identifying serrated lesions of the colon in addition to morphological features.

Co-occurrence of subacute granulomatous thyroiditis and papillary microcarcinoma.

Subacute thyroiditis, which is most commonly observed after a viral infection and may heal spontaneously, is an inflammatory thyroid disease. The co-occurrence of subacute thyroiditis and papillary carcinoma is quite rare. A 58-year-old male patient who applied to our hospital with the complaints of sore throat and neck swelling was performed total thyroidectomy following physical examination, ultrasound, and laboratory analysis. In histopathological examination, many granuloma structures were observed in both lobes, and a papillary microcarcinoma focus of 2 mm in diameter was seen in the left lobe. The co-occurrence of subacute thyroiditis and papillary carcinoma was deemed worthy of presentation as it is rarely observed.

Protective role of misoprostol against cisplatin-induced ototoxicity.

Cis-diammineedichloroplatinum (cisplatin) is a chemotherapeutic agent that is widely used in the treatment of many cancers. Nephrotoxicity, ototoxicity and neurotoxicity are dose-limiting adverse effects for cisplatin. The cellular and molecular mechanisms underlying cisplatin-induced ototoxicity aren't fully understood. It has been proposed that cisplatin primarily cause damage at the cochlea, outer hair cells in particular, leading to excessive production of free oxygen radicals in the organ of Corti, stria vascularis, spiral ligament, and spiral ganglionic cells. The cytotoxicity is associated with the generation of reactive oxygen species (ROS); thus, there is an increasing interest on antioxidants with an effort to discover the established protection against cisplatin-induced ototoxicity over time. Misoprostol (MP) has gained considerable interest as a reactive oxygen species scavenger in recent years. To best of our knowledge, there is no study about protective effect of MP, a prostaglandin E1 (PGE1) analogue, on cisplatin-induced ototoxicity. In our study, we show that protective effects of misoprostol on cisplatin-induced ototoxcity on rats.

Terlipressin-induced ischemic skin necrosis: a rare association.

BACKGROUND: Terlipressin is a synthetic vasopressin analogue that is used in the treatment of bleeding esophageal varices and hepatorenal syndrome in patients with cirrhosis. Serious ischemic adverse events, such as skin necrosis involving the extremities, scrotum, trunk, and abdominal skin, are rarely observed. In the literature to date, 20 cases that developed ischemic skin necrosis due to terlipressin usage have been reported. CASE REPORT: We report a patient with extensive skin necrosis on the infusion site of the right forearm and hand, which developed after the use terlipressin used to treat bleeding oesophageal varices in a 65-year-old man with cirrhosis. CONCLUSIONS: Although rare, ischemic complications of terlipressin do occur.