Article

Problematic issues in the staging of endometrial, cervical and vulval carcinomas.

Department of Cellular Pathology, Birmingham Women's NHS Trust, Birmingham, UK.
Histopathology (Impact Factor: 3.3). 01/2013; 62(1):176-202. DOI: 10.1111/his.12058
Source: PubMed

ABSTRACT The International Federation of Gynecology and Obstetrics (FIGO) staging of tumours of the uterine corpus, cervix and vulva was revised in 2009. The greatest impact of the revised staging was on carcinomas of the uterine corpus. Uterine sarcomas are now staged separately. Changes to the staging system for vulvar carcinomas largely reflect the significance of lymph node status. Only minor amendments have been introduced for cervical carcinomas, which remain the only gynaecological tumours to be staged clinically. These revisions, based on recent evidence, require careful, more detailed assessment of several histological parameters at each anatomical site. The present review deals with the evidence and rationale underpinning the revisions, and includes practical guidance on tumour staging. This covers the assessment and measurement of myoinvasion and evaluation of cervical, parametrial, serosal and vaginal involvement in carcinomas of the uterine corpus; the identification and accurate measurement of stromal invasion in cervical and vulvar carcinomas; the assessment of unusual variants of carcinoma at each of these sites; and the assessment of lymph node involvement.

2 Followers
 · 
109 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription-polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Translational oncology 04/2015; 358(2). DOI:10.1016/j.tranon.2015.01.003 · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early invasive squamous carcinomas of the cervix are sometimes multifocal. There are few guidelines regarding how to measure multifocal carcinomas and options include measuring from the edge of 1 invasive focus to the edge of the furthest invasive focus, adding the maximum horizontal dimension of each invasive focus together or regarding multiple foci as representing distinct small areas of invasion and if clearly separate measure them individually. For tumors with a shallow depth of invasion (<3 mm), this has implications for staging and management because if the maximum horizontal dimension is taken from the edge of 1 invasive focus to the edge of the furthest invasive focus, this could represent a International Federation of Gynaecology and Obstetrics (FIGO) 1B1 carcinoma, whereas alternatively these could be regarded as separate foci of 1A1 disease. It has been our practice to regard such lesions as representing multiple foci of invasion (multifocal FIGO 1A1 carcinomas) if clearly separate, arbitrarily defined by us as a minimum of 2 mm between each separate focus of invasion. In this study, we have obtained follow-up in a series of "multifocal 1A1 cervical squamous carcinomas" treated by local excisional methods (large loop excision of transformation zone or cone biopsy) with margins clear of premalignant and malignant disease. The study included 22 cases, 11 of which (50%) would have been regarded as FIGO stage 1B1 if the horizontal dimension had been measured from the edge of 1 invasive focus to the edge of the furthest invasive focus. In none of the cases was there evidence of recurrence of premalignant or malignant disease during follow-up (9-91 mo; mean and median 48 and 45.5 mo, respectively). Although limited by a relatively small number of cases, our results support the hypothesis that with regard to tumor staging and management, it is best to consider multifocal lesions as representing separate individual foci of invasion, to measure each focus separately, and to determine the FIGO stage on the basis of the highest FIGO stage of an individual focus.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2014; DOI:10.1097/PGP.0b013e31829040ce · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cervical cancers/CCs are one of the commonest malignancies and the second leading cause of cancer-related death in women. Resveratrol inhibits CC cell growth but its molecular target(s) remains unclear. Since the signaling pathways mediated by STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa) cells were analyzed. The biological significances of the above signaling for HeLa and SiHa cells were evaluated by treating the cells with STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia were examined by tissue microarray-based immunohistochemical staining. The results revealed that HeLa and SiHa cells treated by 100μM resveratrol showed extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt activations. Growth inhibition and apoptosis were found in HeLa and SiHa populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical staining performed on the tissue microarrays showed that the frequencies of Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as β-catenin nuclear translocation in CC samples were significantly higher than that of noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and Notch signaling are frequently co-activated in human CC cells and specimens and resveratrol can concurrently inhibit those signaling activations and meanwhile lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest and apoptosis. STAT3 signaling is more critical for CC cells and is the major target of resveratrol because selective inhibition of STAT3 rather than Wnt or Notch activation commits SiHa and HeLa cells to apoptosis.
    Genes & cancer 05/2014; 5(5-6):154-64.

Preview

Download
6 Downloads