Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma: Pattern A predicts excellent survival

Vivian M Spaans, Daniëlla A Scheunhage, Bianca Barzaghi, Cor D de Kroon, Gert J Fleuren, Tjalling Bosse, Ekaterina S Jordanova

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations.

METHODS: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated.

RESULTS: Of 82 AC, 22% showed pattern A, 37% pattern B, and 41% pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95%CI 1.16-12.11, and HR 5.08, 95%CI 1.23-20.98, respectively).

CONCLUSIONS: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.

Original languageEnglish
Pages (from-to)196-201
Number of pages6
JournalGynecologic Oncology
Volume151
Issue number2
DOIs
Publication statusPublished - Nov 2018

Cite this

Spaans, Vivian M ; Scheunhage, Daniëlla A ; Barzaghi, Bianca ; de Kroon, Cor D ; Fleuren, Gert J ; Bosse, Tjalling ; Jordanova, Ekaterina S. / Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma : Pattern A predicts excellent survival. In: Gynecologic Oncology. 2018 ; Vol. 151, No. 2. pp. 196-201.
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title = "Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma: Pattern A predicts excellent survival",
abstract = "OBJECTIVE: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations.METHODS: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated.RESULTS: Of 82 AC, 22{\%} showed pattern A, 37{\%} pattern B, and 41{\%} pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95{\%}CI 1.16-12.11, and HR 5.08, 95{\%}CI 1.23-20.98, respectively).CONCLUSIONS: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.",
keywords = "Adenocarcinoma/genetics, Adult, Female, Humans, Lymphatic Metastasis, Middle Aged, Mutation, Neoplasm Invasiveness, Prognosis, Retrospective Studies, Uterine Cervical Neoplasms/genetics",
author = "Spaans, {Vivian M} and Scheunhage, {Dani{\"e}lla A} and Bianca Barzaghi and {de Kroon}, {Cor D} and Fleuren, {Gert J} and Tjalling Bosse and Jordanova, {Ekaterina S}",
note = "Copyright {\circledC} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
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language = "English",
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Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma : Pattern A predicts excellent survival. / Spaans, Vivian M; Scheunhage, Daniëlla A; Barzaghi, Bianca; de Kroon, Cor D; Fleuren, Gert J; Bosse, Tjalling; Jordanova, Ekaterina S.

In: Gynecologic Oncology, Vol. 151, No. 2, 11.2018, p. 196-201.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Independent validation of the prognostic significance of invasion patterns in endocervical adenocarcinoma

T2 - Pattern A predicts excellent survival

AU - Spaans, Vivian M

AU - Scheunhage, Daniëlla A

AU - Barzaghi, Bianca

AU - de Kroon, Cor D

AU - Fleuren, Gert J

AU - Bosse, Tjalling

AU - Jordanova, Ekaterina S

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/11

Y1 - 2018/11

N2 - OBJECTIVE: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations.METHODS: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated.RESULTS: Of 82 AC, 22% showed pattern A, 37% pattern B, and 41% pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95%CI 1.16-12.11, and HR 5.08, 95%CI 1.23-20.98, respectively).CONCLUSIONS: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.

AB - OBJECTIVE: Recently, the pattern of invasion in usual-type human papillomavirus-associated endocervical adenocarcinoma (AC) was put forward as a novel variable to select patients with favourable prognosis. Based on destructiveness of stromal invasion, three patterns were proposed: A - no destructive stromal invasion, B - focal destructive stromal invasion, and C - diffuse destructive stromal invasion. We aimed to independently validate the clinical significance of this classification-system in 82 AC patients, and explored associations between invasion pattern and somatic mutations.METHODS: All patients surgically treated for FIGO stage IB-IIA usual type AC (1990-2011, n = 82) were retrospectively reviewed and classified into pattern A, B or C. Additional immunohistochemical analyses were performed for p53, MSH6, and PMS2. Moreover, previously obtained data on somatic hotspot mutations in 13 relevant genes was integrated.RESULTS: Of 82 AC, 22% showed pattern A, 37% pattern B, and 41% pattern C. Significant differences were observed between invasion patterns and tumour size, depth of invasion (DOI), lymph-vascular invasion (LVI), and lymph-node metastasis. Significantly fewer mutations were present in tumours with pattern A morphology (p = 0.036). All pattern A patients survived (p = 0.002) without recurrent disease (p = 0.005). In multivariate regression analysis including tumour size, DOI, LVI, and lymph node metastasis, invasion pattern was a strong independent predictor for recurrence-free and disease-specific survival (HR 3.75, 95%CI 1.16-12.11, and HR 5.08, 95%CI 1.23-20.98, respectively).CONCLUSIONS: We have independently validated the clinical significance of invasion patterns for usual type endocervical AC. Pattern A predicts excellent survival, and a clinical trial should prove safety of a more conservative treatment for these patients.

KW - Adenocarcinoma/genetics

KW - Adult

KW - Female

KW - Humans

KW - Lymphatic Metastasis

KW - Middle Aged

KW - Mutation

KW - Neoplasm Invasiveness

KW - Prognosis

KW - Retrospective Studies

KW - Uterine Cervical Neoplasms/genetics

U2 - 10.1016/j.ygyno.2018.09.013

DO - 10.1016/j.ygyno.2018.09.013

M3 - Article

VL - 151

SP - 196

EP - 201

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -