Subdividing ovarian and peritoneal serous carcinoma into moderately differentiated and poorly differentiated does not have biologic validity based on molecular genetic and in vitro drug resistance data

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Abstract

Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinmas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.

Original languageEnglish (US)
Pages (from-to)1667-1674
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume32
Issue number11
DOIs
StatePublished - Nov 2008

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Drug Resistance
Molecular Biology
Carcinoma
In Vitro Techniques
Mutation
Gynecology
Pharmaceutical Preparations
Obstetrics
Ovary

Keywords

  • Grade
  • Moderately differentiated
  • Ovary
  • Poorly differentiated
  • Serous carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery
  • Medicine(all)

Cite this

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title = "Subdividing ovarian and peritoneal serous carcinoma into moderately differentiated and poorly differentiated does not have biologic validity based on molecular genetic and in vitro drug resistance data",
abstract = "Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as {"}invasive low-grade micropapillary serous carcinoma,{"} is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinmas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84{\%} of moderately and 70{\%} of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.",
keywords = "Grade, Moderately differentiated, Ovary, Poorly differentiated, Serous carcinoma",
author = "Vang, {Russell S} and Shih, {Ie Ming} and Ritu Salani and Elizabeth Sugar and Ayse Ayhan and Kurman, {Robert J}",
year = "2008",
month = "11",
doi = "10.1097/PAS.0b013e31816fd555",
language = "English (US)",
volume = "32",
pages = "1667--1674",
journal = "American Journal of Surgical Pathology",
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T1 - Subdividing ovarian and peritoneal serous carcinoma into moderately differentiated and poorly differentiated does not have biologic validity based on molecular genetic and in vitro drug resistance data

AU - Vang, Russell S

AU - Shih, Ie Ming

AU - Salani, Ritu

AU - Sugar, Elizabeth

AU - Ayhan, Ayse

AU - Kurman, Robert J

PY - 2008/11

Y1 - 2008/11

N2 - Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinmas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.

AB - Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinmas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.

KW - Grade

KW - Moderately differentiated

KW - Ovary

KW - Poorly differentiated

KW - Serous carcinoma

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