A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases

Shiho Kuji, Reiko Watanabe, Yuichi Sato, Takashi Iwata, Yasuyuki Hirashima, Munetaka Takekuma, Ichiro Ito, Masato Abe, Ryo Nagashio, Katsuhiro Omae, Daisuke Aoki, Toru Kameya

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker. Methods Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections. Results In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%). Conclusions This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.

Original languageEnglish
Pages (from-to)384-390
Number of pages7
JournalGynecologic Oncology
Volume144
Issue number2
DOIs
Publication statusPublished - 2017 Feb 1

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Neuroendocrine Carcinoma
Insulinoma
Cervix Uteri
Proteins
Papillomavirus Infections
Neuroendocrine Tumors
Neural Cell Adhesion Molecules
Chromogranin A
Synaptophysin
Zinc Fingers
Paraffin
Formaldehyde
Transcription Factors
Multivariate Analysis
Genotype
Staining and Labeling
Polymerase Chain Reaction

Keywords

  • Cervical cancer
  • Human papillomavirus
  • INSM1
  • Insulinoma associated protein 1
  • Neuroendocrine carcinoma
  • Small cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix : Analysis of 37 cases. / Kuji, Shiho; Watanabe, Reiko; Sato, Yuichi; Iwata, Takashi; Hirashima, Yasuyuki; Takekuma, Munetaka; Ito, Ichiro; Abe, Masato; Nagashio, Ryo; Omae, Katsuhiro; Aoki, Daisuke; Kameya, Toru.

In: Gynecologic Oncology, Vol. 144, No. 2, 01.02.2017, p. 384-390.

Research output: Contribution to journalArticle

Kuji, S, Watanabe, R, Sato, Y, Iwata, T, Hirashima, Y, Takekuma, M, Ito, I, Abe, M, Nagashio, R, Omae, K, Aoki, D & Kameya, T 2017, 'A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases', Gynecologic Oncology, vol. 144, no. 2, pp. 384-390. https://doi.org/10.1016/j.ygyno.2016.11.020
Kuji, Shiho ; Watanabe, Reiko ; Sato, Yuichi ; Iwata, Takashi ; Hirashima, Yasuyuki ; Takekuma, Munetaka ; Ito, Ichiro ; Abe, Masato ; Nagashio, Ryo ; Omae, Katsuhiro ; Aoki, Daisuke ; Kameya, Toru. / A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix : Analysis of 37 cases. In: Gynecologic Oncology. 2017 ; Vol. 144, No. 2. pp. 384-390.
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abstract = "Objective High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker. Methods Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections. Results In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86{\%}, 86{\%} and 68{\%}, respectively. In addition, INSM1 was detected in 95{\%}. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72{\%} of 29 examined cases had high risk HPV infections (type 16, 14{\%}; type 18, 86{\%}). Conclusions This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.",
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T1 - A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix

T2 - Analysis of 37 cases

AU - Kuji, Shiho

AU - Watanabe, Reiko

AU - Sato, Yuichi

AU - Iwata, Takashi

AU - Hirashima, Yasuyuki

AU - Takekuma, Munetaka

AU - Ito, Ichiro

AU - Abe, Masato

AU - Nagashio, Ryo

AU - Omae, Katsuhiro

AU - Aoki, Daisuke

AU - Kameya, Toru

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Objective High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker. Methods Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections. Results In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%). Conclusions This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.

AB - Objective High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker. Methods Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections. Results In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%). Conclusions This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.

KW - Cervical cancer

KW - Human papillomavirus

KW - INSM1

KW - Insulinoma associated protein 1

KW - Neuroendocrine carcinoma

KW - Small cell carcinoma

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