Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels. METHODS: A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system. RESULTS: Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response. CONCLUSION: Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.

Comprehensive immunohistochemical analysis based on the origin of leiomyosarcoma.

Diagnostic criteria, biological behavior, and treatment approaches of leiomyosarcomas (LMS) may differ according to the origin of the tumor. This is important in terms of patient's management, especially in tumors located in the peritoneum and retroperitoneal sites. In our study, we aimed to demonstrate the immunophenotypic characteristics of uterine and extra-uterine LMS using a large antibody panel, and to determine whether they potentially play a role in the differences among these tumor groups. Between 2006 and 2018, 29 uterine and 42 extra-uterine primary LMS were included in this study. Using tissue samples taken from the areas that best represented the tumor, an immunohistochemical study was performed on the blocks prepared by tissue micro-array method with estrogen and progesterone receptor (PR), WT-1, SMA, desmin, caldesmon, calponin, p16, p53, MDM2, CDK4, bcl-2, cyclin D1, fascin, EMMPRIN, FOXM1, c-erb-B2, c-Myc, PAX8, and CD117. Staining results of uterine and extra-uterine LMS were evaluated with these 20 antibodies. In uterine LMS compared with extra-uterine LMS, estrogen receptor (48% vs. 12%), PR (62% vs. 21%), desmin (79% vs. 50%), and EMMPRIN (69% vs. 45%) staining rate was detected higher. In extra-uterine LMS, caldesmon (88% vs. 69%), c-Myc (33% vs. 10%), and cyclin D1 (52% vs. 28%) were stained higher than uterine LMS (p < 0.05). No significant staining difference was detected with other antibodies. We concluded that estrogen receptor, PR, desmin, EMMPRIN, caldesmon, c-Myc, and cyclin D1 antibodies may help to determine primary origin of the tumor in LMS cases.

Clinical Value of CXCL5 for Determining of Colorectal Cancer

Background: Several studies indicate that chemokines play important roles in colorectal mucosal immunity. The chemokine CXCL5 which is expressed by epithelial cells within colorectal mucosa is a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer. The purpose of this study was to investigate whether serum and tissue CXCL5 levels is altered in colorectal carcinomas (CRC) compared to colonic adenoma and normal mucosa.It also aimed to compare colon adenoma and colorectal cancer for blood CXCL5 and CEA levels, their sensitivity, and specificity. Methods: CXCL5 expression was assessed with immunohistochemistry staining in biopsy samples taken during colonoscopy in 22 colonic adenomas, 23 colorectal carcinomas and 23 normal colonic tissue samples. Also all patients' serum CXCL5 and CEA levels were measured. This stduy was prospective observational study. Results: The number of cases who were stained positive with immunohistochemistry was found to be higher in the group with CRC. When compared with the other groups, both levels of serum CXCL5 and CEA were significantly high in the group CRC. Sensitivity and specificity of serum CXCL5 were found to be low as a result of the ROC analysis. Conclusion: Although the level of CXCL5 is high in CRC, its level in serum is not significant enough to support the early diagnosis of the disease.

Polycarbonate and polystyrene nanoplastic particles act as stressors to the innate immune system of fathead minnow (Pimephales promelas).

Water pollution with large-scale and small-scale plastic litter is an area of growing concern. Macro-plastic litter is a well-known threat to aquatic wildlife; however, the effects of micro-sized and nano-sized plastic particles on the health of organisms are not well understood. Small-scale plastic particles can easily be ingested by various aquatic organisms and potentially interfere with their immune system; therefore, the authors used a freshwater fish species as a model organism for nanoplastic exposure. Characterization of polystyrene (41.0 nm) and polycarbonate (158.7 nm) nanoplastic particles (PSNPs and PCNPs, respectively) in plasma was performed, and the effects of PSNPs and PCNPs on the innate immune system of fathead minnow were investigated. In vitro effects of PSNPs and PCNPs on neutrophil function were determined using a battery of neutrophil function assays. Exposure of neutrophils to PSNPs or PCNPs caused significant increases in degranulation of primary granules and neutrophil extracellular trap release compared to a nontreated control, whereas oxidative burst was less affected. The present study outlines the stress response of the cellular component of fish innate immune system to polystyrene and polycarbonate nanoparticles/aggregates and indicates their potential to interfere with disease resistance in fish populations. Environ Toxicol Chem 2016;35:3093-3100. © 2016 SETAC.

EMMPRIN (CD147) Expression in Smooth Muscle Tumors of the Uterus.

Smooth muscle tumors of the uterus are the most common mesenchymal tumors of the gynecologic tract. The vast majority of these are benign leiomyomas that present no diagnostic difficulty. Because some benign smooth muscle tumors may degenerate and uncommon variants exist, the diagnosis can be challenging in some cases. The goal of this research was to investigate EMMPRIN expression in leiomyomas, leiomyoma variants, and leiomyosarcomas (LMS) to determine whether it has a potential role in differential diagnosis. EMMPRIN expression was investigated with immunohistochemistry in 103 uterine smooth muscle tumors, which included 19 usual leiomyomas, 52 leiomyoma variants, and 32 LMS. They were evaluated on the basis of staining extent, intensity, and also their combined score, and the groups were compared. EMMPRIN expression was present in 3 of 19 (15.7%) usual leiomyomas, 23 of 52 (44.3%) leiomyoma variants, and 28 of 32 (87.5%) LMS. There were statistically significant differences in staining extent and intensity, and also for their combined scores, between the LMS and benign groups. Although uterine smooth muscle tumors are usually diagnosed easily with conventional diagnostic criteria, the differentiation of LMS from some variants of leiomyoma can be challenging based soley on morphology. EMMPRIN may be a valuable immunohistochemical marker for differentiating LMS from benign smooth muscle tumors in problematic cases.

Expression of Glypican 3 in low and high grade urothelial carcinomas.

BACKGROUND: Glypican-3 (GPC3) is an oncofetal protein which is encoded by GPC3 gene and takes role in the regulation of cell division and apoptosis. Overexpression of GPC3 has been reported in some types of cancer such as hepatocellular carcinoma (HCC), melanoma, squamous cell carcinoma of the lungs and testicular germ cell tumors. The aim of this study was to investigate the immunohistochemical expression of GPC3 in the non-neoplastic urothelium and in urothelial carcinoma (UC). We also aimed to explore the alterations in the GPC3 expression according to the grade and the invasiveness of UC. METHODS: GPC3 expression was studied in 108 UC cases by using immunohistochemistry. Each section was evaluated in terms of the extensiveness and intensity of GPC3 staining. Scores of immunostaining were correlated with tumor grade and stage. RESULTS: GPC3 expression was observed in 38 cases (35.2%). GPC3 expression was positive in 43.6% of high and in 13.3% of low grade UC (p: 0.003). In 19 UC cases biopsy also harbored non-neoplastic urothelium which showed no staining for GPC3. The difference in staining percentages between low and high grade UCs, suggests that GPC3 staining could be used as an adjunctive marker in cases where the distinction between the low and high grade tumors is difficult. In addition, lack of staining in the non-neoplastic urothelial areas in 19 cases raises the possibility of the use of GPC3 staining for the distinction between neoplastic and non-neoplastic urothelium, especially in punch biopsy samples. CONCLUSIONS: Based on our results potential role of GPC3 in urothelial carcinogenesis warrants further investigation, especially the potential use of GPC3 for therapeutic and diagnostic purposes. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2260833001522844.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

OBJECTIVES: The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. MATERIALS AND METHODS: An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. RESULTS: Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. CONCLUSIONS: In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors.

Co-existence of a large ovarian hemangioma and microscopic dysgerminoma in a 10-year old child.

Ovarian hemangioma is an uncommon ovarian tumor occurring in patients in different age groups. It is usually seen as small, asymptomatic mass, which is detected incidentally. On rare occasions, this type of tumor can be associated with other gynecological neoplasms. In this report, we present the clinicopathologic features of a case of ovarian hemangioma coexisting with multiple microscopic foci of dysgerminoma in a 10-year-old child. The patient presented with acute abdomen. Magnetic resonance imaging revealed a left ovarian mass and subsequent left salpingo-oophorectomy was performed. Grossly, the mass was 9.5 cm in diameter and contained hemorrhage and necrosis. Microscopic examination showed that the tumor was mostly composed of hemangioma. Additionally, there were three microscopic foci of dysgerminoma between the hemangioma and ovarian cortex. Immunohistochemical studies showed that dysgerminoma foci were positive for PLAP, Oct4 and CD117. To our knowledge, this is the first case of the above-described association ever reported.

A rare clinical presentation of sarcoidosis; gingivitis.

Gingivitis due to sarcoidosis is a relatively rare condition. Gingivitis or isolated gingival involvement may be the first sign of systemic sarcoidosis. We report the case of a 37 year-old woman with isolated gingivitis due to sarcoidosis confirmed by biopsy. Following treatment with a systemic corticosteroid (prednisolone 40 mg/day), all clinical and radiologic findings were completely improved. In cases of chronic and intractable gingivitis, systemic sarcoidosis should be suspected. It should be confirmed with a biopsy, and the patient should be referred to a chest disease clinic to exclude other organ involvement.

Thymosin ß4 is a novel potential prognostic marker in gastrointestinal stromal tumors.

Thymosin beta-4 (Tß(4)) is a major actin-sequestering molecule that contributes to cell growth, differentiation, motility, survival, mitosis and angiogenesis. It is overexpressed in certain type of carcinoma and fibrosarcoma cell lines and is associated with metastatic potential. The aim of this study was to investigate the relationship between Tß(4) expression and clinicopathologic features and VEGF status in gastrointestinal stromal tumors (GISTs). Retrospectively, 60 GISTs were re-examined and immunohistochemistry for Tß(4) and VEGF was performed. Increased expression of Tß(4) and VEGF was observed in 26 (43.3%) and in 19 (31.6%) of the tumors, respectively. Tß(4) expression was positively correlated with VEGF expression (p < 0.01). Tß(4) and VEGF expression were significantly associated with tumor size (p = 0.00 and p = 0.02, respectively) and high mitosis (p = 0.03 and p = 0.00, respectively). Although Tß(4) expression was positively associated with pleomorphism (p = 0.01), VEGF expression was positively associated with necrosis (p = 0.03). Tß(4) expression was related with local recurrence and/or metastasis (p = 0.03), but VEGF expression was not (p = 0.12). We firstly demonstrate the presence of Tß(4) protein in GISTs. Our study reveals that increased expression of Tß(4) could be considered as an indicator of aggressive behavior of tumor.

UbcH10 expression in benign, hyperplastic, and malignant endometrial curetted materials: a tissue microarray study.

The aim of this study was to investigate the role of UbcH10 expression in the differential diagnosis of benign, hyperplastic, and malignant endometrial tissues and also the relationship of UbcH10 with the clinicopathologic parameters of malignant cases. A tissue microarray was performed for 81 endometrial curettage biopsies, which histological diagnosis had demonstrated to be 13 cases of proliferative endometrium, 7 cases of disordered proliferative endometrium, 5 cases of complex atypical hyperplasia, 24 cases of nonatypical hyperplasia, and 32 cases of endometrioid adenocarcinoma. Expression of UbcH10 was assessed by immunohistochemistry. When groups were compared according to UbcH10 percentages and scores, a statistically significant difference was found only between the carcinoma group and the other groups, except the complex atypical hyperplasia group (P < .05). In the malignant group, UbcH10 percentages and scores were only significantly related to age. There was no significant association between UbcH10 expression and tumor grade and stage. Overexpression of UbcH10 may be a useful indicator of endometrial carcinoma. UbcH10 also deserves further evaluation in the detection of prognostic mean and also for its role in endometrial carcinogenesis.

Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.

Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

Giant fibrolipoma with osseous metaplasia on the thigh.

Fibrolipomas are characterised by fat lobules embedded in perivascular oval fibrocytes and thick bundles of collagen. Actively growing superficial fibrolipomas rarely display a pedunculated protrusion and, thus, cosmetic and functional problems are uncommon. We present an exceptional case. While trauma and ischaemia can lead to fibrosis and dystrophic calcification in fibrolipomas as late sequelae, osseous and cartilaginous metaplasia can infrequently manifest after a long, chronic persistence. Further, depending on the chronic irritation, ulcerated wounds may develop on the surface, and these can be clinically confused with malignancy. In this article, we present a case of a pedunculated giant fibrolipoma manifesting metaplasic changes in its structure.

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx.

UNLABELLED: The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx. METHODS: We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored. RESULTS: The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively). CONCLUSIONS: Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas.

Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and inhibitors as well as on interactions with the extracellular matrix. We examined the immunohistochemical expression of the defining angiogenic agents, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), and the antiangiogenic agent thrombospondin-1 (TSP-1) in 131 patients with urothelial carcinoma and correlated their expression levels with clinicopathological parameters. VEGF and MMP-9 expression was higher in high-grade tumors than in low-grade tumors (p=0.000 and p=0.001, respectively), whereas the reverse was true for TSP-1 (p=0.000). VEGF and MMP-9 expression was higher in deeper tumors compared to superficial tumors and in invasive tumors compared to non-invasive tumors (p=0.001 and p=0.001, respectively), while TSP-1 was lower (p=0.000). We could differentiate 22 of 41 muscle-invasive (T2) cases as superficial (T2a; n=7) or deep (T2b; n=15), but no difference was found between them regarding VEGF, MMP-9, or TSP-1 expression (p=0.783, p=0.289, and p=0.783, respectively). There was a positive correlation between VEGF and MMP-9 expression (p=0.008, r=0.23) but a negative correlation between MMP-9 and TSP-1 expression (p=0.014, r=-0.21). Increased VEGF and MMP-9 expression as well as decreased TSP-1 expression may play considerable roles in the invasion and differentiation of urothelial carcinoma.

Rare association of Hirschsprung's disease and Joubert syndrome.

We present the case of an 18-month-old boy with Hirschsprung's disease who had psychomotor retardation. His clinical and radiological findings were consistent with Joubert syndrome. The patient was the second case to show the association between Hirschsprung's disease and Joubert syndrome in the literature. As in our case, association of these entities by chance seems to be unlikely. Genetic analysis of new Joubert syndrome and Hirschsprung's disease patients may identify the candidate genes.

Hypohidrotic ectodermal dysplasia with true anodontia of the primary dentition.

Ectodermal dysplasia is a rare congenital hereditary entity. The most commonly observed forms of ectodermal dysplasia are the hidrotic and hypohidrotic types; discrimination is based on the absence or presence of sweat glands. In this report, a child with hypohidrotic ectodermal dysplasia having true anodontia of the primary dentition is presented. Physical, mental, and intraoral examinations were performed. Photographs and occlusal and panoramic radiographs were taken. A medical consultation and biopsies were requested. Mentally, the patient was normal. His hair and eyebrows were light colored and sparse. He had frontal bossing, a saddle nose, reduced vertical facial dimension, and prominent supraorbital ridges and chin. Radiographs revealed absence of all primary and permanent teeth except the bilaterally unerupted maxillary permanent canines. An armpit biopsy specimen revealed the absence of eccrine and apocrine glands. A removable prosthesis was made to satisfy the patient's esthetic and functional needs. The absence of primary teeth (true anodontia) is a rare phenomenon. It is claimed that primary teeth must be present for the development of their permanent successors. In the present case, however, the permanent canines existed despite the absence of their predecessors. Dental clinicians can be the first to diagnose ectodermal dysplasia. The dental team should be aware of its signs and symptoms in order to provide the correct therapies for the functional and psychologic needs of these patients.

Renal amyloidosis due to pulmonary tuberculosis in a patient with Down syndrome.

A pulmonary-tuberculosis-related renal amyloidosis patient with Down syndrome, who presented with nephrotic syndrome, was studied.