Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression

A Gynaecological Oncology Group Study

S. Y. Liao, W. H. Rodgers, J. Kauderer, K. M. Darcy, R. Carter, N. Susumu, S. Nagao, J. L. Walker, M. Hatae, E. J. Stanbridge

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. Methods: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16 INK 4 a (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. Results: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. Conclusion: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalBritish Journal of Cancer
Volume108
Issue number3
DOIs
Publication statusPublished - 2013 Feb 19

Fingerprint

Hyperplasia
Neoplasms
Papillomavirus Infections
Proteins
Papanicolaou Test
Mucinous Adenocarcinoma
Carbonic Anhydrase IX
Cervix Uteri
Cell Biology
Stomach
Carcinogenesis
Biomarkers
Phenotype
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression : A Gynaecological Oncology Group Study. / Liao, S. Y.; Rodgers, W. H.; Kauderer, J.; Darcy, K. M.; Carter, R.; Susumu, N.; Nagao, S.; Walker, J. L.; Hatae, M.; Stanbridge, E. J.

In: British Journal of Cancer, Vol. 108, No. 3, 19.02.2013, p. 613-620.

Research output: Contribution to journalArticle

Liao, S. Y. ; Rodgers, W. H. ; Kauderer, J. ; Darcy, K. M. ; Carter, R. ; Susumu, N. ; Nagao, S. ; Walker, J. L. ; Hatae, M. ; Stanbridge, E. J. / Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression : A Gynaecological Oncology Group Study. In: British Journal of Cancer. 2013 ; Vol. 108, No. 3. pp. 613-620.
@article{68fd9350db6941eaa520a83157c57e20,
title = "Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: A Gynaecological Oncology Group Study",
abstract = "Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. Methods: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16 INK 4 a (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. Results: Out of 12 (83{\%}) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100{\%}) cases. P16 protein expression was observed in 11 out of 12 (92{\%}) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62{\%}) showed focal weak (1+) p16 expression. In contrast, all cases (100{\%}) exhibited strong CA-IX protein expression. Conclusion: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.",
author = "Liao, {S. Y.} and Rodgers, {W. H.} and J. Kauderer and Darcy, {K. M.} and R. Carter and N. Susumu and S. Nagao and Walker, {J. L.} and M. Hatae and Stanbridge, {E. J.}",
year = "2013",
month = "2",
day = "19",
doi = "10.1038/bjc.2012.578",
language = "English",
volume = "108",
pages = "613--620",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression

T2 - A Gynaecological Oncology Group Study

AU - Liao, S. Y.

AU - Rodgers, W. H.

AU - Kauderer, J.

AU - Darcy, K. M.

AU - Carter, R.

AU - Susumu, N.

AU - Nagao, S.

AU - Walker, J. L.

AU - Hatae, M.

AU - Stanbridge, E. J.

PY - 2013/2/19

Y1 - 2013/2/19

N2 - Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. Methods: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16 INK 4 a (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. Results: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. Conclusion: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.

AB - Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. Methods: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16 INK 4 a (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. Results: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. Conclusion: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.

UR - http://www.scopus.com/inward/record.url?scp=84875229171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875229171&partnerID=8YFLogxK

U2 - 10.1038/bjc.2012.578

DO - 10.1038/bjc.2012.578

M3 - Article

VL - 108

SP - 613

EP - 620

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 3

ER -