Programmed Death Ligand-1 (PD-L1) expression is up-regulated and related to the pattern of invasion in FIGO Stage I vulvar squamous cell carcinomas

The immune checkpoint protein programmed death ligand-1 (PD-L1) is expressed in different types of cancer and is a potential prognostic factor as well as therapeutic target. This study evaluated PD-L1 expression in the neoplastic progression of vulvar epithelia with respect to the pattern of infiltration in FIGO stages I keratinizing squamous cell carcinomas (SCC). Normal squamous vulvar epithelia (n=20), usual type vulvar intraepithelial neoplasia (uVIN, n=23), differentiated VIN (dVIN, n=21) and FIGO stage I SCC (n=35) were immunostained for PD-L1. In SCC a cohesive growth with well-delineated borders was considered as pushing, dissociative growth in small groups or single cells was defined as diffuse pattern of infiltration. Immunostaining was done with a monoclonal anti PD-L1 antibody (clone SP263, Ventana) and scored to determine up-regulation and overexpression (score 0/1+, 0-5% immunoreactive cells; score 2+, >5 to 50% immunoreactive cells; score 3+, >50% immunoreactive cells). PD-L1 immunoexpression was comparable in normal epithelia and VINs (score 0/1+, n=59; score 2+, n=5, in VINs only; score 3+, n=0), was significantly increased (P<0.0001) in SCC (score 0/1+, n=13; score 2+, n=16; score 3+, n=6), and was related to a diffuse pattern of infiltration (P<0.0001). Staining was accentuated at the invasive margins of SCC frequently. PD-L1 expression is up-regulated in the neoplastic cells of vulvar low stage SCC, related to the development of an invasive phenotype reflecting the initiation of cancer immunoediting, and to an aggressive diffuse type of stromal invasion

Bilateral serous tubal intraepithelial carcinoma associated with high-grade serous carcinoma of the peritoneum: evidence for transcoelomic tumor spread by extended lymph node evaluation

Serous tubal intraepithelial carcinoma (STIC) is now considered a putative precursor lesion of most extrauterine high-grade serous carcinomas (HGSC). It is frequently reported in high-risk women and women with advanced-stage serous carcinoma. This case study reports a serous high-grade carcinoma (HGSC) consisting of a bilateral STIC with a focus of stromal invasion in the left tube, and a peritoneal HGSC. The grossly normal-appearing tubes including the fimbriated ends were sectioned following the SEE-FIM protocol. In both tubes, tumor aggregates were exfoliated extensively to the tubal lumens. The neoplastic epithelia in any location were diffusely positive for p53 in strong nuclear patterns. Pelvic lymph nodes were negative for tumor on serial sections and keratin 7 immunohistochemistry, and there was no evidence of lymphatic vessel involvement. The lack of any evidence of lymphovascular invasion and regional lymph node metastases supports the interpretation of intraluminal and transcoelomic spread, and may be taken as evidence of dissemination of tubal neoplastic cells by exfoliation in this case. The biology of transcoelomic spread is reviewed in this manuscript

Undifferentiated Endometrial Sarcoma of the Ovary: A Case Report with Review of Recent Literature and Discussion of Lacking Specificity of CD10 Immunoreactivity

Undifferentiated endometrial sarcomas (UESs) of the ovary are very rare tumors. This paper presents a case of a 56-year-old patient with a history of hysterectomy and bilateral salpingectomy seven years ago for uterine leiomyomata. Intraoperatively, a tumor originating from the left ovary, adherent to the sigmoid colon, with infiltration of the small intestine and the vaginal apex was found. Histologically, the tumor was composed of pleomorphic round and oval to spindled cells with polymorphous vesicular nuclei with coarse chromatin and large nucleoli. Mitotic activity was brisk. There were large necrotic areas. Adjacent to the tumor tissue endometrium-like glands surrounded by fibrous stroma with macrophages corresponding to ovarian endometriosis were noted. Tumor cells showed diffuse strong immunoreactivity for vimentin and patchy strong staining for CD10; no reactivities were found for AE1/AE3, desmin, S-100, LCA, CD20, c-kit, and CD31. The patient died of her neoplastic disease four months postoperatively. CD10 is frequently expressed in different gynecopathological as well as other lesions, and, thus, nonspecific without relevance to the classification of this case. Morphological features, extensive sampling, and appropriate immunohistochemistry including markers for cytokeratins and myogenic differentiation are mandatory to arrive at the correct diagnosis

Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors

Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has beendescribed. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes

The accuracy of frozen section analysis in ultrasound- guided core needle biopsy of breast lesions

<p>Abstract</p> <p>Background</p> <p>Limited data are available to evaluate the accuracy of frozen section analysis and ultrasound- guided core needle biopsy of the breast.</p> <p>Methods</p> <p>In a retrospective analysis data of 120 consecutive handheldultrasound- guided 14- gauge automated core needle biopsies (CNB) in 109 consecutive patients with breast lesions between 2006 and 2007 were evaluated.</p> <p>Results</p> <p>In our outpatient clinic120 CNB were performed. In 59/120 (49.2%) cases we compared histological diagnosis on frozen sections with those on paraffin sections of CNB and finally with the result of open biopsy. Of the cases 42/59 (71.2%) were proved to be malignant and 17/59 (28.8%) to be benign in the definitive histology. 2/59 (3.3%) biopsies had a false negative frozen section result. No false positive results of the intraoperative frozen section analysis were obtained, resulting in a sensitivity, specificity and positive predicting value (PPV) and negative predicting value (NPV) of 95%, 100%, 100% and 90%, respectively. Histological and morphobiological parameters did not show up relevance for correct frozen section analysis. In cases of malignancy time between diagnosis and definitive treatment could not be reduced due to frozen section analysis.</p> <p>Conclusion</p> <p>The frozen section analysis of suspect breast lesions performed by CNB displays good sensitivity/specificity characteristics. Immediate investigations of CNB is an accurate diagnostic tool and an important step in reducing psychological strain by minimizing the period of uncertainty in patients with breast tumor.</p

BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence

BACKGROUND:The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes. OBJECTIVE:To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival. MATERIALS AND METHODS:Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function. RESULTS:High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03). CONCLUSIONS:Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance