The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors.

BACKGROUND: Primary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. METHODS: Seventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. RESULTS: Mutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). CONCLUSION: p53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Rate of Incidental Pathological Lesions in Reduction Mammoplasty Specimens and Incidence of Invasive Breast Carcinoma Following Breast Reduction Operation.

INTRODUCTION: Reduction mammoplasty (RM) is one of the most frequently performed surgical procedures. The incidental determination of significant pathologic lesions (SPL), that is precursor and malignant lesions, in RM specimens is rare. The aim of this study was to determine the frequency of SPL in RM specimens, to evaluate the relationship between SPL and clinicopathological factors, and to examine the incidence of invasive breast carcinoma forming in the remaining breast tissue during the postoperative follow-up period developing in patients after RM operation. MATERIAL AND METHOD: This retrospective study included 874 females who underwent RM operation between January 2012 and January 2021. Demographic, clinicopathological findings, and preoperative radiological findings were recorded. The patients were followed up after the RM operation in respect of the first occurrence of breast cancer. RESULTS: Invasive carcinoma was determined in 0.2% and SPL in 3.5% in RM. The probability of SPL determination was greater in patients aged ≥ 40 years and with ≥ 4 paraffin blocks (p=0.038, p=0.01, respectively). No statistically significant difference was found between patients with and without SPL in respect of radiological findings (p=0.35). The mean postoperative follow-up period was 53.6 months, and invasive carcinoma was diagnosed during follow-up in 0.2% of all patients (6.9% of the patients with SPL). CONCLUSION: Age over 40 years and an increased number of sampled blocks were found to be factors increasing the possibility of the determination of precursor and malignant lesions in RM specimens. RM could decrease the risk of the development of breast cancer. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HMGB1 expression in urothelial carcinoma of the bladder.

PURPOSE: HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in urothelial carcinoma of bladder (UCB) or not. METHODS: The study included 90 cases that were histopathologically diagnosed with UCB in the tissue samples obtained by transurethral resection (TUR). HMGB1 expression was investigated by immunohistochemistry. RESULTS: A total of 90 patients, 80 (88.9%) male and 10 (11.1%) female, were enrolled in the study. The histopathological diagnosis was infiltrating urothelial carcinoma (IUC) in 63 (70.0%) and non-invasive papillary urothelial carcinoma (NIPUC) in 27 (30.0%). When the NIPUC cases were grouped according to grade, 24 (88.9%) of the cases were low grade and 3 (11.1%) were high grade. HMGB1 expression was found positive in 51 (56.7%) and negative in 39 (43.3%) of the patients. HMGB1 expression was significantly higher in IUCs (p=0.046). CONCLUSION: The results of our study demonstrate that HMGB1 overexpression has a significant role in UCB progression and it corroborates the idea that it might be an important prognostic factor.

Retrospective Evaluation of Children with Congenital Pulmonary Airway Malformation: A Single Center Experience of 20 Years.

OBJECTIVES: Congenital pulmonary airway malformation (CPAM) is an uncommon congenital abnormality of the lungs that generally presents during prenatal period or early childhood. In this study, we aimed to evaluate clinical and pathologic findings of the children with CPAMs who were referred to our center between 1992 and 2011. MATERIAL AND METHODS: We reviewed 19 children with CPAM, who were diagnosed and treated at the Izmir Dr. Behçet Uz Children's Hospital between 1992 and 2011. All of them are alive and have been still followed up by our center. RESULTS: The study population consisted of 9 boys (47.4%) and 10 girls (52.6%) with a mean age of 3.26 (1 month - 13 years). Most newborns had respiratory distress, while recurrent pulmonary infections were detected in older children. Surgical treatment was performed on patients with subtypes I (n = 4; 21.1%), II (n = 8; 42.1%), III (n = 5; 26.3%), and IV (n = 2; 10.5%). In 13 cases (63.4%), lesions were located in the right lung and in almost all cases lesions were confined to one lobe. A one-month- old child with type I CPAM had multiple lesions involving two lobes and in only a newborn with type II CPAM, lesions were located bilaterally. There was no type 0 cases in this series. All cases were treated with lobectomy without any complication. CONCLUSION: In the present study, a realistic comprehensive picture of CPAM in a central children's hospital has been provided. In addition, we want to emphasize that complications and unnecessary medical treatment could be reduced with early surgery.

Massive pericardial effusion due to intrapericardial mixed germ cell tumor in a premature baby.

Primary cardiac tumor is uncommon in childhood, with an incidence of 0.06-0.32%, and intrapericardial teratoma represents an exceptional rarity among these entities. Germ cell tumors (GCT) are rare, representing only 1-3% of childhood tumors. Twenty per cent of GCT are malignant and are associated with age and location. Extragonadal involvement accounts for nearly half of the cases. Anterior mediastinum is a common location of malignant germ cell tumors, yet pericardial and aortic adventitia involvement have been rarely reported. Here we report the case of a preterm twin baby boy with intrapericardial mixed germ cell tumor who presented with hydrops fetalis and pericardial effusion.

Expression of caveolin-1 in peritumoral stroma is associated with histological grade in ovarian serous tumors.

BACKGROUND: Previous studies have demonstrated that Caveolin-1 (Cav-1) can ambiguously behave as tumor suppressor or tumor promoter in different neoplasms, depending on cancer type. Some findings have also revealed that cell proliferation, migration and invasion were attenuated by the knockdown of Caveolin-1 expressions. However, the functional and prognostic significance of Caveolin-1 in most tumors remains to be fully elucidated. OBJECTIVES: The aim of the study was to investigate a possible association between tissue Caveolin-1 expression and the clinicopathologic features of ovarian serous tumors. MATERIAL AND METHODS: Caveolin-1 expression was studied in a total of 82 formalin-fixed, paraffin-embedded specimens of ovarian serous tumors and its association with different clinicopathologic parameters was evaluated. RESULTS: The study included 36 (43.9%) benign, 12 (14.6%) borderline and 34 (41.5%) malignant serous tumors. Mean patient age was 43.9 ± 14.4 years (17-72 years). Statistical analysis revealed that if the tumor becomes more aggressive and invasive, it losses the stromal Caveolin-1 expression (p = 0.001). Also, parallel changes between stromal and perivascular Caveolin-1 expressions were observed. CONCLUSIONS: Our findings demonstrated a link between Caveolin-1 expression and the aggressiveness of ovarian cancer. Therefore, it seems safe to suggest that Cav-1 may act as a differential diagnostic biomarker in ovarian serous tumors.

Acute generalized exanthematous pustulosis induced by ceftriaxone use.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous rash characterized by the abrupt onset of a generalized pustular rash often accompanied by fever. There is a history of drug use in 90% of the cases. Here we have reported a 15-year-old male patient with sickle cell anemia who developed AGEP after the use of ceftriaxone. Our patient was hospitalized because of vaso-occlusive crisis and on the third day of ceftriaxone treatment, erythematous pustular lesions accompanied with fever were observed on the body and extremities. Resolution of symptoms followed discontinuation of ceftriaxone. Sensitivity to ceftriaxone was shown with a patch test. The AGEP was considered due to clinical and histopathological findings. This is the first pediatric case of AGEP due to ceftriaxone.

ß­catenin expression in endometrioid type endometrial cancer: Expression patterns and impact on disease outcomes.

Determination of nuclear and/or cytoplasmic expression of ß-catenin by immunohistochemistry in patients with endometrial cancer (EC) may constitute a potential diagnostic method for identifying patients with a catenin ß1 (CTNNB1) gene mutation and those at risk of disease recurrence. The present study aimed to investigate ß-catenin expression patterns in hysterectomy specimens of patients with endometrioid type EC using immunohistochemistry, and to examine the prognostic impact of ß-catenin. The study was a single-institutional, retrospective cohort trial enrolling consecutive patients with a postoperative histopathological diagnosis of endometrioid EC who underwent hysterectomy between January 2015 and December 2018. Histopathology slides from 75 patients were stained with a monoclonal antibody targeting the ß-catenin protein. Any percentage of nuclear staining, whether focal or diffuse, was considered 'ß-catenin nuclear-positive'. The cytoplasmic staining reaction of ß-catenin was assessed based on the percentage of stained cells and staining intensity. Immune-reactivity score (IRS) values were determined by multiplying the scores for the percentage of staining and staining intensity. IRS values 0 to 2 were regarded as negative expression, 3 to 4 as low expression, 6 to 8 as moderate expression, and 9 to 12 as high expression. Recurrence-free survival (RFS) was used as the prognostic endpoint. Only 2 out of 75 tissue samples (2.7%) exhibited nuclear ß-catenin expression, with a low staining percentage of 5%. By contrast, cytoplasmic staining was observed in all samples (100%). According to the IRS findings, 1.3% of the samples exhibited negative cytoplasmic expression, 42.7% low expression, 38.7% moderate expression and 17.3% high expression. Cox regression analysis revealed that staining with ß-catenin, either nuclear or cytoplasmic, had no impact on RFS, and stage was the sole independent prognostic factor. In conclusion, based on these results, ß-catenin expression in endometrioid EC was revealed to be mostly cytoplasmic, with only 2.7% of tissue samples exhibiting nuclear expression. Overall, ß-catenin expression has no impact on RFS.

Expression of p16 in pterygium and its relation with epithelial dysplasia and possible etiologic role of HPV.

Context: p16 is an important tumor suppressor gene and responsible for regulating the cell cycle. Diffuse positivity with p16 in the cervix and head/neck carcinomas can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). Aim: The aim of our study was to search the existence of p16 expression in pterygium. We also analyzed the association of p16 expression with epithelial dysplasia and HPV expression. Subjects and Methods: The study enrolled 75 cases of pterygium. The conjunctival tissues of 10 patients excised by the strabismus surgery were used as control group. All of the slides were stained with p16 via the immunohistochemical method. Results: 49 (65%) of pterygiums showed low-grade epithelial dysplasia. None of the control groups showed dysplasia. Positive expression of p16 in patient group was significantly higher (P < 0.001). Staining percentage (SP) of p16 was between 0 and 26% in pterygium; mean SP was 5.1%. There was no staining in the control group. A total of 59 (72%) pterygium cases were positive with p16. Appoximately 42 of 49 (85%) cases with dysplasia showed p16 staining. There was a significant relation between dysplasia and positive expression of p16 (P < 0.001). Conclusions: P16 is significantly expressed in pterygium and correlated with epithelial dysplasia. Furthermore, the existence of p16 expression suggests that HPV is a possible ethiological factor in pterygium. We think that examination of p16 expression and analysis of HPV DNA in p16 positive cases can help us to understand the etiopathogenesis of the disease better.

The extent of cyclin D1 expression in endometrial pathologies and relevance of cyclin D1 with the clinicopathological features of endometrioid endometrial carcinoma.

BACKGROUND: Cyclin D1, a member of the cyclin protein family, is instrumental in the cell cycle due to its influence on the progression from G1 to the S phase. Its overexpression causes reduced doubling time and is also associated with clonogenic growth. The purpose of the present study was to assess cyclin D1 expression in patients with simple hyperplasia (SH), endometrial intraepithelial neoplasia (EIN) and endometrioid endometrial carcinoma, and to evaluate whether there was an association between cyclin D1 expression and the clinicopathological features of endometrioid endometrial carcinoma. METHODS: Retrospective data were available for 193 patients (30 SH, 40 EIN, and 123 endometrioid endometrial carcinoma cases). To detect cyclin D1 expression, immunohistochemistry staining was performed with tissue microarrays. RESULTS: The percentage of cases with positive cyclin D1 staining were 30%, 60% and 78%, for SH, EIN and endometrioid endometrial carcinoma, respectively (P < 0.001). Carcinomas with higher nuclear grade, histological grade, and FIGO grade displayed higher mean cyclin D1 expression compared to lower grade carcinomas. In addition, patients with lymphovascular invasion (P = 0.006), myometrial invasion (P < 0.001) and lymph node invasion (P < 0.001) had higher mean cyclin D1 expression compared to those without invasion. There was a significant correlation between cyclin D1 expression and clinicopathological features of endometrioid endometrial carcinoma including tumor grade, FIGO grade, lymphovascular invasion, lymph node invasion and myometrial invasion (P < 0.05 for each). CONCLUSION: Cyclin D1 expression is significantly higher in patients with endometrioid endometrial carcinoma compared to that of the SH and EIN. The extent of cyclin D1 expression is strongly correlated with nuclear and histological grade, myometrial invasion, lymphovascular invasion and lymph node invasion in patients with endometrioid endometrial carcinoma. These findings contribute in several ways to our understanding of cyclin D1 expression and provide a basis for future research on this topic.

The diagnostic significance of trophoblast cell-surface antigen-2 expression in benign and malignant thyroid lesions.

CONTEXT: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. AIMS: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. SUBJECTS AND METHODS: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. RESULTS: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). CONCLUSION: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.

Effect of a new cross-linked hyaluronan gel on the staple line after sleeve gastrectomy in a rat model.

PURPOSE: To evaluate the effect of a new cross-linked hyaluronan (NCHA) gel on healing of the staple line in an experimental sleeve gastrectomy. METHODS: Eighteen rats were randomly divided into three groups. The control group (n = 6) received no medication. In the saline group (n = 6) and NCHA gel group (n = 6), saline and NCHA gel were respectively administered onto the staple line and intraperitoneally into the abdominal cavity after the standard stapling procedure. RESULTS: The fibroblast activity and collagen deposition were significantly higher in the NCHA gel group than in the control group (p = 0.00, p = 0.017) and saline group (p = 0.004, p = 0.015). The tissue hydroxyproline protein level was significantly higher in the NCHA gel group than in the control group (p = 0.041). Adhesion formation was significantly lower in the NCHA gel group than in the control and saline groups (p = 0.015, p = 0.041). CONCLUSIONS: New cross-linked hyaluronan gel could be an effective approach to improve staple line wound healing and prevent potential leakage after sleeve gastrectomy. Moreover, NCHA gel helps to prevent adhesion formation without compromising healing of the staple line.

Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Wilms Tumor.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) and Kidney injury molecule-1 (KIM-1) play important roles in both immunity and cell proliferation. It was reported previously that they are overexpressed in various human cancers. The present study was undertaken to examine the expressions of NGAL and KIM-1 in Wilms Tumors. MATERIAL AND METHOD: Tissue samples of 50 Wilms Tumors were evaluated and underwent immunhistochemical staining for NGAL and KIM-1 protein expressions. The correlations between them, and some clinical prognostic factors such as tumor weight, stage and histological features were also evaluated. RESULTS: Twenty-three (46%) of the cases were male while 27 (54%) were female. The mean age was found to be 3.26±2 years. The average tumor size was 9.16 ± 2.9 cm in diameter and the average weight of the kidney was 478±312 gr. Thirteen (26%) cases were stage I, 18 (36%) cases were stage II, 7 (14%) cases were stage III, and 6 (12%) cases were stage IV. Thirty-nine cases were alive (78%), while 11 cases (22%) were deceased. Mean overall survival time was 68.2±39.5 (2-148) months. NGAL expression was negative in all tumors except the neutrophils within the tumors. KIM-1 expression was positive in 37 tumors (74%), while it was absent in 13 tumors (26%). Using Mann-Whitney U Analysis, KIM-1 expression was found to be associated with the stage of the tumor (p=0.027). CONCLUSION: The preliminary data indicates that KIM-1 expression may be associated with stage in Wilms Tumor. However, further studies are needed to validate these pilot observations and to clarify the functional and mechanistic significance of this relevance.

Histopathological and genetic features of patients with limb girdle muscular dystrophy type 2C.

OBJECTIVE: In this study, it was aimed to describe the clinical, histopathological and genetic features of 20 patients with gamma sarcoglycanopathy confirmed by muscle biopsies and genetic analysis. MATERIAL AND METHOD: We retrospectively reviewed 20 patients from whom muscle biopsy specimens were obtained between 2007 and 2012. All patients were clinically diagnosed as muscular dystrophy and biopsy materials were collected from five different centers of neurological disorders. All DNAs were extracted from muscle tissues or blood samples of patients and genetic tests (mutation analyses for gamma sarcoglycan gene and deletion-duplication analyses for all 4 sarcoglycan genes) were performed. RESULTS: The mean age of the patients was 7.6 years (2 -21 years). Only one case (5%) was older than 14 years. The mean CPK level was 10311 U/L (1311 - 35000 U∕L). There were 4 siblings in these series. Expression defects of gamma sarcoglycan staining were determined in (15 males, and 5 females) all patients with muscle biopsy specimens. But only in 9 of them, disease-causing defects could be determined with genetic analyses. CONCLUSION: The present study has demonstrated that both examination of muscle biopsy specimens and DNA analysis remain important methods in the differential diagnosis of muscular dystrophies. Because dystrophinopathies and sarcoglycanopathies have similar clinical manifestation.