open access

Vol 88, No 12 (2017)
Review paper
Published online: 2017-12-29
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Molecular diagnosis in type I epithelial ovarian cancer

Paweł Sadłecki1, Małgorzata Walentowicz-Sadłecka1, Marek Grabiec1
DOI: 10.5603/GP.a2017.0123
·
Pubmed: 29303228
·
Ginekol Pol 2017;88(12):692-697.
Affiliations
  1. Katedra i Klinika Połoznictwa, Chorób Kobiecych i Ginekologii Onkologicznej Collegium Medicum UMK w Bydgoszczy, ul. Ujejskiego 75, 85-168 Bydgoszcz, Poland

open access

Vol 88, No 12 (2017)
REVIEW PAPERS Gynecology
Published online: 2017-12-29

Abstract

The term epithelial ovarian cancer (EOC) refers to a heterogeneous group of tumors, including serous, mucinous, endometrioid and clear cell carcinomas, each characterized by specific molecular background and clinical outcome. A growing body of evidence suggests that molecular pathogenesis of ovarian cancer involves two general pathways. The first pathway results in transformation of normal ovarian tissue to borderline tumors, which may further progress to low-grade serous, mucinous, endometrioid and clear cell carcinomas. Tumors from this group are characterized by slow proliferation, and approximately 55% 5-year survival rate. Type I tumors often harbor somatic mutations in protein kinase genes, as well as in genes for other signaling molecules. Both BRAF and KRAS mutations lead to a constitutive activation of their downstream target, mitogen-activated protein kinase. Identification of molecular profile may be crucial for the diagnosis of ovarian tumors, choice of adjuvant targeted therapy after primary cytoreductive treatment, or management of recurrence in patients with advanced type I epithelial ovarian neoplasms. Point mutations in cancer cells can be detected with many various methods. KRAS, NRAS and BRAF mutational status can be determined by Sanger sequencing (still considered a gold standard), as well as using numerous various techniques, such as allele-specific PCR, single nucleotide primer extension assays, pyrosequencing, real-time PCR, high-resolution melting curve analysis, amplification refractory mutation system, strip or chip assay combining PCR followed by hybridization to a KRAS or NRAS-specific probe, next-generation sequencing (NGS), and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Application of direct sequencing as a routine method for cytological diagnosis used in a hospital setting requires expensive equipment and implementation of complicated procedures. Another factor limiting application of this method in everyday clinical practice are long analytical times. This stimulated search for a simple, rapid, specific and sensitive methodology to detect point mutations. Recently, some new molecular assays for the detection of BRAF, KRAS and NRAS mutations have become available. These are fully-automated molecular diagnostic systems for quantitative allele-specific RT-PCR-based analyses. Using this instrument, even pathologists from less experienced laboratories can easily integrate morphological findings with molecular data being crucial for further diagnostic and therapeutic decisions.

Abstract

The term epithelial ovarian cancer (EOC) refers to a heterogeneous group of tumors, including serous, mucinous, endometrioid and clear cell carcinomas, each characterized by specific molecular background and clinical outcome. A growing body of evidence suggests that molecular pathogenesis of ovarian cancer involves two general pathways. The first pathway results in transformation of normal ovarian tissue to borderline tumors, which may further progress to low-grade serous, mucinous, endometrioid and clear cell carcinomas. Tumors from this group are characterized by slow proliferation, and approximately 55% 5-year survival rate. Type I tumors often harbor somatic mutations in protein kinase genes, as well as in genes for other signaling molecules. Both BRAF and KRAS mutations lead to a constitutive activation of their downstream target, mitogen-activated protein kinase. Identification of molecular profile may be crucial for the diagnosis of ovarian tumors, choice of adjuvant targeted therapy after primary cytoreductive treatment, or management of recurrence in patients with advanced type I epithelial ovarian neoplasms. Point mutations in cancer cells can be detected with many various methods. KRAS, NRAS and BRAF mutational status can be determined by Sanger sequencing (still considered a gold standard), as well as using numerous various techniques, such as allele-specific PCR, single nucleotide primer extension assays, pyrosequencing, real-time PCR, high-resolution melting curve analysis, amplification refractory mutation system, strip or chip assay combining PCR followed by hybridization to a KRAS or NRAS-specific probe, next-generation sequencing (NGS), and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Application of direct sequencing as a routine method for cytological diagnosis used in a hospital setting requires expensive equipment and implementation of complicated procedures. Another factor limiting application of this method in everyday clinical practice are long analytical times. This stimulated search for a simple, rapid, specific and sensitive methodology to detect point mutations. Recently, some new molecular assays for the detection of BRAF, KRAS and NRAS mutations have become available. These are fully-automated molecular diagnostic systems for quantitative allele-specific RT-PCR-based analyses. Using this instrument, even pathologists from less experienced laboratories can easily integrate morphological findings with molecular data being crucial for further diagnostic and therapeutic decisions.
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Keywords

low grade ovarian cancer, type 1 ovarian cancer, borderline ovarian tumors, KRAS mutation, BRAF mutation, NRAS mutation

About this article
Title

Molecular diagnosis in type I epithelial ovarian cancer

Journal

Ginekologia Polska

Issue

Vol 88, No 12 (2017)

Article type

Review paper

Pages

692-697

Published online

2017-12-29

DOI

10.5603/GP.a2017.0123

Pubmed

29303228

Bibliographic record

Ginekol Pol 2017;88(12):692-697.

Keywords

low grade ovarian cancer
type 1 ovarian cancer
borderline ovarian tumors
KRAS mutation
BRAF mutation
NRAS mutation

Authors

Paweł Sadłecki
Małgorzata Walentowicz-Sadłecka
Marek Grabiec

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