Dataset Information

The roles of pathology in targeted therapy of women with gynecologic cancers.

ABSTRACT: The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor. Therefore, expanding the arsenal of available systemic therapies with targeted therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the treatment of advanced gynecologic cancer, and many more are under investigation. Pathologists remain important in the clinical management of patients with targeted therapy, by identifying potentially targetable tumors on the basis of their pathologic phenotype, by assessing biomarkers that are predictive of response to targeted therapy (e.g. microsatellite instability, PD1/PDL1 expression), and by monitoring treatment response and resistance. Pathologists are also vital to research efforts exploring novel targeted therapies by identifying homogenous subsets of tumors for more reliable and meaningful analyses, and by confirming expression in tumor tissues of novel targets identified in genomic, epigenetic or other screening studies. In the era of precision gynecologic oncology, the roles of pathologists in the discovery, development and implementation of targeted therapeutic strategies remain as central as they are for traditional (surgery-chemotherapy-radiotherapy) management of women with gynecologic cancers.

SUBMITTER: Murali R

PROVIDER: S-EPMC5756523 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

The roles of pathology in targeted therapy of women with gynecologic cancers.

Murali Rajmohan R Grisham Rachel N RN Soslow Robert A RA

Gynecologic oncology 20171123 1

The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatmen ...[more]

PMID: 29174566

Similar Datasets

Project description:Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.

Dataset Information

The roles of pathology in targeted therapy of women with gynecologic cancers.

Publications

The roles of pathology in targeted therapy of women with gynecologic cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure