Nuclei Of Neoplastic Cells Research Articles

A Rare Case of Triple-Negative Breast Cancer with RAD51D Gene Mutation

Background: The heterogeneity of breast cancer (BC) subtypes poses a significant challenge, with carcinogenesis involving multiple stages and genes, including proto-oncogenes, tumor suppressor genes, and DNA repair genes. Next-generation sequencing has expanded access to multigene panels, such as RAD51 paralogs, which increase the risk of ovarian cancer and possibly triple-negative (TN) BC. Case presentation: We present a rare case of a 45-year-old woman with TNBC and a RAD51D gene mutation. Mammography and breast ultrasonography revealed an irregular, 30 mm hypoechoic area and dystrophic calcifications in the right breast. Immunohistochemistry showed a lack of expression of ER, RP, HER-2, and P53, with 50% of neoplastic cell nuclei positive for Ki-67. Next-generation sequencing revealed a mutation in RAD51D and MUYTH genes. The patient underwent partial mastectomy, chemotherapy, and prophylactic mastectomy. Conclusion: Genetic analysis is crucial for identifying specific mutations contributing to TNBC development. Current preventive interventions primarily address BRCA1 and BRCA2 mutations, following established guidelines.

Mammary carcinoma in a male cat following long-term medroxyprogesterone acetate treatment: case report and review of the literature.

In male cats, as in men, mammary carcinomas are rarely reported. However, like in females, hormonal therapy is a significant risk factor. This study reports the case of an 11-year-old male cat with multiple mammary tumours and a history of long-term medroxyprogesterone acetate therapy for the suppression of sexual behaviour, along with a brief review of the literature. Complete surgical removal of the right mammary chain and the ipsilateral inguinal lymph nodes was performed, and all tissues were submitted for histology. Histological examination revealed the presence of a tumour in the third and fourth mammary glands, consisting of neoplastic cells arranged in various structures, including tubulopapillary and tubular structures, sometimes cystically dilated, and solid areas. The inguinal lymph nodes were also involved. The morphology was consistent with a diagnosis of mammary carcinoma, tubulopapillary type, with nodal metastases. Immunohistochemistry revealed that tumour cells were positive for cytokeratin (clones AE1/AE3), while stromal cells were positive for vimentin (clone V9). The proliferation marker Ki-67, evaluated on both the primary tumour and the nodal metastases, was strongly expressed in the nuclei of neoplastic cells, with a Ki-67 proliferation index of 8.9% and 20% for the primary tumour and the metastases, respectively. This case highlights the importance of considering the possibility of malignant mammary tumours not only in female but also in male cats with a history of long-term hormonal treatment for suppression of sexual behaviour.

ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

Histopathological and Immunohistochemical Studies of a Spontaneous Case of Pulmonary Adenomatosis in an Adult Ram: A Case Report

Aim: The present study aimed to describe histopathological findings and immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in a spontaneous case of pulmonary adenomatosis in an adult ram. Case Presentation: A carcass of an adult ram was presented for necropsy in the Post-mortem Hall of the Department of Veterinary Pathology, College of Veterinary Sciences of the Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar with a history of respiratory distress. A detailed necropsy was performed. The tracheal mucosa showed mild congestion. The lungs were pale and firm in consistency. On histopathological examination, nasal turbinate and trachea both showed the vascular changes along with mild infiltration of mononuclear cells. The sections of lungs revealed pulmonary adenocarcinoma characterized by the presence of cuboidal to low columnar epithelial cells forming acinar or papillary-like structures in the parenchyma and surrounded by the normal alveoli. Areas of necrosis along with infiltration of mononuclear cells were also evident. An Immunohistochemical study of the lung sections revealed mild to moderate immunopositive reactivity for the PCNA in the nuclei of neoplastic cells of adenocarcinoma. It indicated the proliferative activity of neoplastic cells. Conclusion: Based on histopathological examination, the present case was diagnosed as pulmonary adenomatosis. PCNA expression indicated the presence of actively proliferating neoplastic cells.

Canine soft tissue sarcomas: the expression of RUNX2 and karyopherin alpha-2 in extraskeletal (soft tissues) and skeletal osteosarcomas.

Extraskeletal osteosarcoma (EOS) is a malignant tumor producing bone matrix and/or chondroid material, without direct attachment to bone or periosteum. In humans and dogs, EOS is highly infiltrating, rapidly growing, often characterized by osteoid deposition and variable ossification, similar to primary skeletal osteosarcoma (SOS). In dogs, EOS arises from visceral and soft tissue locations, occasionally in trauma or foreign body sites, or in granulomas. Few data are currently available on the phenotype of these tumors. The present study aims to assess the expression RUNX2 and Karyopherin alpha-2 in EOS, comparing it with SOS and the data available from the human counterpart. Seventeen cases of canine osteosarcoma (13 EOS and 4 SOS) were retrospectively selected and submitted to immunohistochemistry for RUNX2 and Karyopherin alpha-2. Our results showed that, in EOS, RUNX2 is expressed in a mean of 73.07 ± 5.36 neoplastic cell nuclei, in face of a mean 36.15 ± 6.25 of Karyopherin alpha-2 positive nuclei. Osteoclasts, when present, were negative for both markers. No correlation was observed among the two markers (p > 0.05), nor statistically significant difference in quantitative expression was assessed comparing EOS and SOS groups. RUNX2 is expressed in canine EOS similarly to SOS and could be used as a diagnostic marker in a larger panel. Karyopherin alpha-2 is expressed in canine EOS and SOS similarly to human SOS and could be validated in future studies as an additional diagnostic marker. Further studies should be planned to evaluate the expression of these proteins as prognostic predictive parameters.

Immunohistochemical characterization of clear cell variant of hepatocellular carcinoma in a sheep

The cadaver and viscera of a mature female sheep (Ovis aries) underwent routine abattoir meat inspection. The liver was expanded by an infiltrative neoplastic mass comprising multifocal to coalescing, well-demarcated, pink to white–yellow nodules, up to 25 mm in diameter. An unencapsulated, moderately densely cellular, infiltrative neoplasm was present within the hepatic parenchyma. The neoplastic cells were arranged in solid sheets and acini supported by a moderately fine collagenous vascularized stroma. The neoplastic cells were moderately sized and polygonal, with clearly delineated cell borders and a moderate amount of cytoplasm that was clear or exhibited either globular eosinophilic deposits or fine fibrillar eosinophilic strands. The neoplastic cell nuclei were round and centrally located. The chromatin was lightly stippled and there was frequently a single, prominent, basophilic nucleolus. There were eight mitoses in 10 high-power fields (2.37 mm2). Most of the neoplastic cells had intense cytoplasmic immunolabelling for arginase 1, with frequent concurrent nuclear positivity, and mild to moderately intense punctate cytoplasmic labelling for hepatocyte specific antigen (Hep Par-1). The neoplastic cells did not label with anti-cytokeratin 19 antibody. Based on the histological appearance and the immunolabelling pattern, the neoplasm was diagnosed as the clear cell variant of a hepatocellular carcinoma.

SMARCB1 (INI-1) – Deficient sinonasal carcinoma: Report of two cases

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare, poorly differentiated carcinoma defined by complete loss of tumor suppressor gene SMARCB1 (INI-1) within the neoplastic cell nuclei demonstrated by the immunohistochemical stain. SMARCB1 (INI-1) gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma was first reported by Agaimy et al. in 2014. These tumors are often basaloid with focal rhabdoid differentiation, prominent necrosis, increased mitotic activity, and aggressive behavior. Other than being INI-1 and NUT negative, they are positive for pancytokeratin and express variable immunoreactivity for squamous markers like p63 and neuroendocrine markers like synaptophysin. Most patients present with locally advanced disease and hence a combination of chemotherapy, radiotherapy, and surgery is usually recommended.

Upregulated MYC expression and p53 mutations may contribute to the oncogenesis of canine Meibomian gland carcinomas.

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma.

Self-renewal of the intestinal epithelium originates from stem cells located at the crypt base. Upregulation of various stem cell markers in intestinal epithelial neoplasms indicates a potential role of stem cells in tumorigenesis. In this study, the immunoreactivity of potential intestinal stem cell markers (Sry box transcription factor 9 [Sox9], homeodomain-only protein [Hopx], survivin) and tuft cell marker doublecortin-like kinase 1 (DCLK1) in normal canine intestine and intestinal epithelial neoplasms was investigated. Formalin-fixed paraffin-embedded (FFPE) small and large intestine as well as intestinal neoplasms (55 colorectal adenomas [CRAs], 17 small intestinal adenocarcinomas [SICs], and 12 colorectal adenocarcinomas [CRCs]) were analyzed immunohistologically. Potential stem cell markers Sox9, Hopx, and survivin were detected in the crypts of normal canine small and large intestine. DCLK1+ tuft cells were present in decreasing numbers along the crypt-villus axis of the jejunum and rarely detectable in large intestine. In canine intestinal epithelial tumors, nuclear Sox9 immunoreactivity was detectable in 84.9% (CRA), 80% (CRC), and 77% of epithelial neoplastic cells (SIC). Hopx and survivin were expressed within cytoplasm and nuclei of neoplastic cells in benign and malignant tumors. DCLK1 showed a cytoplasmic reaction within neoplastic cells. The combined score of Hopx, DCLK1, and survivin varied among the examined cases. Overall, malignant tumors showed lower DCLK1 scores but higher Hopx scores in comparison with benign tumors. For survivin, no differences were detectable. In conclusion, stem cell markers Sox9, Hopx, and survivin were detectable at the crypt base and the immunoreactivity of Sox9, DCLK1, survivin, and Hopx was increased in canine intestinal adenomas and adenocarcinomas compared with normal mucosa.

Tumor-specific overexpression of histone gene, H3C14 in gastric cancer is mediated through EGFR-FOXC1 axis

Incorporation of different H3 histone isoforms/variants have been reported to differentially regulate gene expression via alteration in chromatin organization during diverse cellular processes. However, the differential expression of highly conserved histone H3.2 genes, H3C14 and H3C13 in human cancer has not been delineated. In this study, we investigated the expression of H3.2 genes in primary human gastric, brain, breast, colon, liver, and head and neck cancer tissues and tumor cell lines. The data showed overexpression of H3.2 transcripts in tumor samples and cell lines with respect to normal counterparts. Furthermore, TCGA data of individual and TCGA PANCAN cohort also showed significant up-regulation of H3.2 genes. Further, overexpressed H3C14 gene coding for H3.2 protein was regulated by FOXC1 transcription factor and G4-cassette in gastric cancer cell lines. Elevated expression of FOXC1 protein and transcripts were also observed in human gastric cancer samples and cell lines. Further, FOXC1 protein was predominantly localized in the nuclei of neoplastic gastric cells compared to normal counterpart. In continuation, studies with EGF induction, FOXC1 knockdown, and ChIP-qPCR for the first time identified a novel axis, EGFR-FOXC1-H3C14 for regulation of H3C14 gene overexpression in gastric cancer. Therefore, the changes the epigenomic landscape due to incorporation of differential expression H3 variant contributes to change in gene expression pattern and thereby contributing to pathogenesis of cancer.

Quantification of Global DNA Methylation in Canine Mammary Gland Tumors via Immunostaining of 5-Methylcytosine: Histopathological and Clinical Correlations.

Mammary tumors are the most prevalent neoplasms in non-neutered female dogs, with genetic and epigenetic alterations contributing to canine mammary carcinogenesis. This study quantified global DNA methylation in 5-methylcytosine (5mC)-immunostained canine mammary tumor samples and established histopathological and clinical correlations. A total of 91 formalin-fixed paraffin-embedded mammary tumor samples from female dogs were retrospectively selected and subjected to immunohistochemistry using an anti-5mC mouse monoclonal antibody. We evaluated 5mC+ stained nuclei of neoplastic epithelial cells in canine mammary glands to obtain semiquantitative histoscores based on staining intensity. Survival rates were estimated based on owners' or veterinary records. Histological samples comprised 28 and 63 benign and malignant canine mammary gland tumors, respectively. Results revealed significant differences between global DNA methylation patterns when mammary samples were categorized as benign or malignant (p = 0.024), with hypomethylated patterns more prevalent in malignant tumors and those with higher relapse behavior (p = 0.011). Of note, large diameter (>5 cm) tumors revealed a lower methylation pattern (p = 0.028). Additionally, we found non-statistically significant differences when tumors were grouped by histopathological characteristics, clinical parameters, or survival. These findings propose global DNA methylation assessment as a promising tool for detecting canine mammary tumors with relapse propensity.

Clinicopathologic study of 6 cases of epithelioid osteoblastoma of the jaws with immunoexpression analysis of FOS and FOSB.

The aim of this study was to describe the clinicopathologic features of a series of gnathic epithelioid osteoblastomas. As high levels of Proto-oncogene c-Fos proteins resulting from FOS-FOSB translocation were recently demonstrated in osteoblastomas, we also evaluated the immunoexpression of these proteins. Records of all cases of epithelioid osteoblastoma of the jaws were retrieved from oral pathology services, and their clinicopathologic and immunohistochemical data were collected. Immunohistochemistry was also performed by using anti-FOS and anti-FOSB antibodies. Six cases of epithelioid osteoblastomas were obtained, 4 in men and 2 in women, and they were mainly located in the posterior body of the mandible (n = 4). Radiographically, the tumors showed mixed radiolucent and radiopaque images, most with poorly defined margins. Microscopically, large epithelioid cells with eccentrically located nuclei predominated among osteoid and immature bone trabeculae. Sharp delineation from adjacent normal bone was observed in all cases. FOS immunostaining was diffuse and strong in the cytoplasm and nucleus of neoplastic cells in all cases, whereas FOSB was only focally positive, with few epithelioid osteoblasts showing nuclear staining. Although epithelioid osteoblastomas of the jaws are locally aggressive, widespread metastasis does not occur, and, as with conventional osteoblastomas, there is wide expression of the FOS protein.

Mycosis Fungoides: A Clinicopathological Study of 60 Cases from a Tertiary Care Center.

Background:Mycosis fungoides (MF) is the most common primary cutaneous lymphoma. It affects usually the covered areas of the body in elderly males in 6th and 7th decades of life. Atypical dermal lymphoid infiltrate is seen along with epidermotropism. Nuclei of neoplastic cells are convoluted. The neoplastic cells demonstrate positivity for CD3 (Pan T) immunohistochemical stain. Majority show increased CD4 to CD8 ratio. The present study was done to study the clinicopathological features, which might be of help in reaching a correct diagnosis in these cases.Materials and Methods:A retrospective descriptive study was conducted on 60 reported cases of MF. The retrieved slides were reviewed for clinical and histopathological features and immunohistochemical profile.Results:The ages ranged from 20–84 years, mean age was 47 years. Majority (75%) of patients were male. Trunk and extremities were the sites most commonly affected. There was significant inverse correlation between epidermal thickness and tumor stage (P = 0.02). Thickened epidermis was seen in patch stage and thickness reduced with progressing stage. The intensity of dermal infiltrate and cell size was also statistically significantly linked to stage progression (P < 0.001 each). In addition, proliferation index also correlated significantly with tumor stage (P = 0.002).Conclusion:Clinical information and histological features are equally important in the accurate diagnosis of MF. Papillary dermal fibrosis is a useful diagnostic clue. CD4:CD8 ratio is not increased in all cases; it may be decreased or remain unchanged.

A Study on Immunohistochemical Expression of Progesterone Receptor and Cell Proliferation by AgNOR in Canine Mammary Tumors (CMT)

Mammary gland tumors are the most commonly diagnosed tumors in domestic dogs. Although immunohistochemical methods provide valuable information such as the location and semi-quantitative data of the interested antigens in particular tumors, conventional methods like histopathological diagnosis remain useful and necessary for identification and classification of tumors. In the present study, we combined histopathology with immunohistochemical staining for progesterone receptor (PR) and special staining argyrophilic nucleolar organizer regions (AgNOR) for cell proliferation in canine mammary gland tumors. Twenty-nine dogs with primary mammary gland neoplasms (11 benign and 18 malignant) were included in this study. All 29 tumors were stained with AgNOR but only 15 cases expressed positive PR signals in the nuclei of neoplastic alveolar and ductal epithelial cells. A weak positive correlation (r = 0.2) was observed between PR and AgNOR index of benign tumors and a very weak negative correlation (r = -0.1833) between PR and AgNOR index of malignant tumors suggesting that higher cellular proliferation is associated with low expression of progesterone receptors.

The cell tube block technique and an immunohistochemistry panel including Wilms tumor 1 to assist in diagnosing cavitary effusions in dogs and cats.

Cell blocks and immunohistochemistry (IHC) are increasingly recognized as being complementary tools for cytologic diagnostics, especially for neoplastic diseases. The study aimed to evaluate the utility of cell tube block (CTB) IHC for refining the diagnosis of effusions in dogs and cats. Cavitary effusions (n=25) from dogs and cats classified by cytology as reactive, neoplastic, borderline (suspicious of neoplasia), and chylous were studied. CTB sections were stained with H&E, and immunostained with PAX-5, CD3, pancytokeratin (CK), vimentin, and Wilms tumor 1 protein (WT1) antibodies, according to the cytologic diagnoses. A histologic case series of confirmed normal, reactive, and neoplastic mesothelium and several different carcinomas were included to test the utility of WT1 as a marker of mesothelial cells. CTBs had a layered appearance with reduced background staining. CD3 and PAX5 immunolabeling allowed immunophenotype assessment in all of the lymphoma cases. In carcinomatous effusions, neoplastic cells were CK-positive, WT1-negative, and vimentin-negative (except for two cases). Wilms tumor 1 protein was positive in the nuclei of normal, reactive, and neoplastic mesothelial cells, and ovarian carcinomatous cells. Other carcinomas and lymphomas were negative. CTBs are valuable tools to assist in making a diagnosis of cavitary effusions in dogs and cats, and WT1 is a promising marker to differentiate mesothelial from carcinomatous cells.

Papillary adenocarcinoma of sweat gland with multiorgan metastases in lion (Panthera leopersica)

A big tumorous mass about 6 inches in diameter was observed on the ventral aspect of neck in a 23 years old lion. Histopathological examination of the biopsy sample revealed it to be adenocarcinoma involving sweat gland. The lion died after 10 days. Postmortem examination followed by histopathology of various organs revealed the neoplastic growth forming the acinar pattern with papillary projections not only in the dermis but also in intercostals skeletal muscles, lungs, liver, kidneys, spleen and intestinal wall. The nuclei of neoplastic cells were hyperchromatic and bizarre shaped with increased nucleus:cytoplasm ratio and had numerous mitotic figures. The neoplastic cells were also seen as emboli in blood vessels of these organs. The cytoplasm of the neoplastic cells was periodic acid-Schiff (PAS) positive. The pancytokeratin and proliferative cell nuclear antigen (PCNA) immune staining were positive in the neoplastic cells. Based on these observations the case was diagnosed as papillary adenocarcinoma of highly anaplastic grade with metastases.

Pseudomyogenic hemangioendothelioma: a little-known tumor

Pseudomyogenic hemangioendothelioma (PHE) is a rare indolent vascular tumor that typically has a multifocal presentation and involves multiple tissue planes. This report describes a 34-year-old man with multiple infiltrated brown papules and plaques on his left leg that had evolved for 6 months. The skin biopsy revealed a dermal and subcutaneous neoplasm composed of fascicles of spindle cells with atypia and epithelioid cells with prominent nucleoli and abundant eosinophilic cytoplasm. There was no evidence of necrosis, and the mitotic rate was low. There was strong reactivity with cytokeratin AE1/AE3, ERG, and FLI1, multifocal reactivity with smooth muscle actin, and focal reactivity with CD31. There was no expression of keratin MNF116, CAM5.2, CD34, CAMTA1, S100-protein, epithelial membrane antigen, melan-A, HMB-45, factor XIIIa, HHV8, or CD10. The nuclei of neoplastic cells showed intact expression of INI1. The clinical, histological, and immunophenotypical aspects were consistent with a diagnosis of PHE. A lower limb CT scan showed lesions in the skin, muscle, and bone planes. The patient was sent to an oncology center, where he maintains regular clinical and imagiological follow-up.

Nrf2-peroxiredoxin I axis in polymorphous adenocarcinoma is associated with low matrix metalloproteinase 2 level.

Polymorphous adenocarcinoma (PAC) is a malignant epithelial neoplasm that affects almost exclusively the minor salivary glands, generally described as having a relatively good prognosis. Aberrant nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) activation in tumor cells has been associated with induction of antioxidant enzymes, such as peroxiredoxin I (Prx I) and increased matrix metalloproteinase (MMP) expression. In this context, the aim of the present study was to evaluate the expression of Nrf2 and correlate it with Prx I and MMP-2 secretion in PAC. Thirty-one cases of PAC from oral biopsies were selected and immunohistochemically analyzed for Nrf2 and Prx I. MMP-2 quantification was performed on primary cell cultures derived from PAC. Oral squamous cell carcinoma (OSCC) cell cultures were used as control. A high immunoexpression of Nrf2 was observed in both the cytoplasm and the nucleus of neoplastic cells from PAC. Nuclear staining for Nrf2 suggested its activation in the majority of the PAC cells, which was confirmed by the high expression of its target gene, Prx I. Quantification of MMP-2 secretion showed lower levels in PAC cell cultures when compared to OSCC cell cultures (p<0.05). In conclusion, although Nrf2 overexpression has been frequently associated with high-grade malignancies, such relationship is not infallible and, in fact, the opposite may occur in low-grade tumors, such as PAC of minor salivary glands.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma

ObjectiveMost molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. MethodsSubjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. ResultsPNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). ConclusionsOne-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

Is the Wnt/β catenin signalling pathway activated in Seminoma?: An immunohistochemical study.

The loss of reduction of some adhesion molecules is associated with the invasive phenotype of carcinomas. The aim of this paper was to study the expression of some proteins related to the Wnt/β catenin signalling pathway in seminomas by immunohistochemical techniques in order to assess the contribution of this pathway to the tumoral development. Immunohistochemistry for E-cadherin, β-catenin, vimentin, C-Myc, cyclin D1 (CD1) and placental alkaline phosphatase. (PALP) was carried out in 24 archival tissue blocks of seminomas. Two cellular lines were used as E-cadherin and β-catenin controls. (JKT-1 and TCam-2). E-cadherin was positive in two seminomas and in one carcinoma in situ. (CIS), showing a membranous pattern. βcatenin was principally expressed in Sertoli cells, in some malignant gonocytes of CIS and in the membranes of seminomatous cells. No β-catenin immunostaining was detectable in the cytoplasm and the nuclei of neoplastic cells. Seminomas were weakly possitive for vimentin in 11/24 cases. None of the tumors displayed expression of C-Myc or CD1. The results does not indicate the activation of the Wnt pathway, due to the lack of vimentin expression in 13/24 seminomas, the low expression in the rest of the cases, the lack of β-catenin in nuclei and the absence of CD1 and C-Myc expression. Further work is needed to confirm these observations and to test other signaling pathways in seminomas.