Fibroadenoma in vulval ectopic breast tissue in a patient with PTEN Hamartoma Tumour Syndrome

PTEN is a tumour suppressor gene involved in regulating cell division. Pathogenic germline variants in PTEN predispose to benign and malignant growths of numerous organs, including of the breast. In the following report, we describe the first documented case of a fibroadenoma developing in ectopic breast tissue of the vulva in a patient with a germline pathogenic variant in PTEN. This highlights the risk of hyperplasia developing in any breast tissue, including rare ectopic sites, particularly in patients with underlying germline variants in cancer susceptibility genes

The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma

Purpose. We sought to identify the genomic abnormalities in squamous cell carcinomas (SCC) arising in ovarian mature cystic teratoma (MCT), a rare gynaecological malignancy of poor prognosis. Experimental design. We performed copy number, mutational state and zygosity analysis of 151 genes in SCC arising in MCT (n=25) using next-generation sequencing. The presence of high/intermediate risk HPV genotypes was assessed by quantitative PCR. Genomic events were correlated with clinical features and outcome Results. MCT had a low mutation burden with a mean of only 1 mutation per case. Zygosity analyses of MCT indicated four separate patterns, suggesting that MCT can arise from errors at various stages of oogenesis. A total of 244 abnormalities were identified in 79 genes in MCT-associated SCC, and the overall mutational burden was high (mean 10.2 mutations per megabase). No SCC was positive for HPV. The most frequently altered genes in SCC were TP53 (20/25 cases, 80%), PIK3CA (13/25 cases, 52%) and CDKN2A (11/25 cases, 44%). Mutation in TP53 was associated with improved overall survival. In 8/20 cases with TP53 mutations, two or more variants were identified, which were bi-allelic. Conclusions. Ovarian SCC arising in MCT has a high mutational burden with TP53 mutation the most common abnormality. The presence TP53 mutation is a good prognostic factor. SCC arising in MCT share similar mutation profiles to other SCC. Given their rarity, they should be included in basket studies that recruit patients with SCC of other organs

NuMA Overexpression in Epithelial Ovarian Cancer

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon

Image guided biopsy in the management of cancer of the ovary

When used in the context of multidisciplinary team discussion, image guided biopsy using ultrasound (US) or computed tomography (CT) guidance is of value in planning management of women with suspected ovarian cancer and peritoneal carcinomatosis (PC) of uncertain aetiology. It is essential in women believed to have ovarian cancer but with poor performance status or with advanced disease believed beyond the scope of primary cytoreductive surgery for whom staging surgical pathology will not be obtained. It provides a site-specific primary tumour diagnosis in 93% of cases and it should replace diagnostic laparoscopy or laparotomy for this purpose. It allows provision of primary (neoadjuvant) chemotherapy based on a firm histological diagnosis. It is mandatory in women with a history of cancer whose metastases may mimic ovarian cancer (e.g. breast, GI tract, melanoma). More women with prior breast cancer who re-present with peritoneal cancer will have a new gynaecological primary than recurrence of their original primary tumour; the two options require radically different therapies. Finally it is a valuable problem solving tool in situations of diagnostic uncertainty, e.g. unusual imaging patterns of disease such as PC with bilateral solid ovarian masses or non-enlarged ovaries and with an unusual tumour marker profiles suggesting primary tumours outwith the ovary. The technique is simple, safe and effective and can be combined with palliative drainage of ascites at the same procedure

Notes & Tips A robust RNA integrity-preserving staining protocol for laser capture microdissection of endometrial cancer tissue

a b s t r a c t Laser capture microdissection of frozen tissue sections allows homogeneous cell populations to be isolated for expression profiling. However, this requires striking a balance between retaining adequate morphology for accurate microdissection and maintaining RNA integrity. Various staining protocols were applied to frozen endometrial carcinoma tissue sections. Although alcohol-based methods were superior to aqueous stains for maintaining RNA integrity, they suffered from irreproducible staining intensity. We developed a modified alcohol-based, buffered cresyl violet staining protocol that provides reproducible staining with minimal RNA degradation suitable for tissues with moderate to high levels of intrinsic RNase activity. Ó LCM has been used extensively on frozen endometrial tissue, although RIN values of extracted RNA are seldom reported. Indeed, to our knowledge, the highest quality RNA obtained through endometrial tissue LCM had a minimum cutoff RIN of 6 were mounted onto room temperature RNase-free glass slides that were immediately placed on dry ice and fixed/stained on the same day. Following staining, whole sections were scraped into RLT buffer (Qiagen, Crawley, UK) containing 2-mercaptoethanol (1%, v/v) and extracted using RNeasy Plus microkits (Qiagen) after homogenization through QIAshredder columns (Qiagen), and RNA was stored at À80°C. To simulate LCM, matched stained sections were kept at ambient temperature for 3 h prior to extraction. For LCM, 12-lm sections were mounted onto polyethylene naphthalate (PEN)-coated slides (Carl Zeiss, Munich, Germany) and 2-4 Â 10 6 lm 2 epithelial cells were microdissected into 500-ll adhesive cap tubes (Carl Zeiss) using the RoboLPC function of a PALM MicroBeam LCM microscope (Carl Zeiss). RNA was extracted as above but without the QIAshredder step and with additional Qiagen RPE buffer and 80% ethanol column washes (one each). Eluted RNA was concentrated using a Savant SC110 SpeedVac with a cold trap for 15-20 min at ambient temperature, and the RNA was redissolved in 5 ll of RNase-free water (to bring the RNA concentration within a measurable range). For all experiments, starting RNA integrity was determined by extracting RNA from a whole unmounted section cut from the same tissue at the same time as the experimental sections. RNA 0003-2697/$ -see front matter

Microcephalin nuclear intensity in the training set.

<p>Microcephalin nuclear intensity in the training set.</p

Correlation of cytoplasmic ASPM expression with clinicopathological data in the EOC validation set.

<p>P≤0.05 is significant and are shown in bold.</p

Einfluesse des Massstabs auf die Kavitation an einem Propeller

SIGLETIB: RA 2207 (175) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Immunohistochemical analysis of Microcephalin and ASPM expression in malignant samples.

<p>Serous adenocarcinoma TMA cores showing nuclear and cytoplasmic Microcephalin (A and B) and ASPM expression (C and D) respectively. White arrow shows nuclear staining and black arrow shows cytoplasmic staining. A and B are 20x, C and D are 40x magnification.</p

Cytoplasmic ASPM levels correlate with various clinic-pathological parameters in EOC.

<p>A. Cytoplasmic ASPM levels decrease with grade in serous EOC (continuous data, p<0.0001). B. Cytoplasmic ASPM levels decrease with tumour grade in the serous subtype (discontinuous data, p = 0.0239). C. Cytoplasmic ASPM levels increase with disease stage in endometrioid EOC (discontinuous data, p = 0.0229). D. Cytoplasmic ASPM levels decrease with disease stage in the serous subtype (discontinuous data, p = 0.0017). E. Cytoplasmic ASPM levels decrease with tumour invasion (discontinuous data, p = 0.02). F. High cytoplasmic ASPM levels correlate with no lymph node involvement (p = 0.04). All data analysed using an ANOVA test.</p