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Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)

Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retr...

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Autores principales: Inzani, Frediano, Santoro, Angela, Angelico, Giuseppe, Feraco, Angela, Spadola, Saveria, Arciuolo, Damiano, Valente, Michele, Carlino, Angela, Piermattei, Alessia, Scaglione, Giulia, Scambia, Giovanni, Rindi, Guido, Zannoni, Gian Franco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281076/
https://www.ncbi.nlm.nih.gov/pubmed/32408525
http://dx.doi.org/10.3390/cancers12051211
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author Inzani, Frediano
Santoro, Angela
Angelico, Giuseppe
Feraco, Angela
Spadola, Saveria
Arciuolo, Damiano
Valente, Michele
Carlino, Angela
Piermattei, Alessia
Scaglione, Giulia
Scambia, Giovanni
Rindi, Guido
Zannoni, Gian Franco
author_facet Inzani, Frediano
Santoro, Angela
Angelico, Giuseppe
Feraco, Angela
Spadola, Saveria
Arciuolo, Damiano
Valente, Michele
Carlino, Angela
Piermattei, Alessia
Scaglione, Giulia
Scambia, Giovanni
Rindi, Guido
Zannoni, Gian Franco
author_sort Inzani, Frediano
collection PubMed
description Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs.
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spelling pubmed-72810762020-06-15 Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5) Inzani, Frediano Santoro, Angela Angelico, Giuseppe Feraco, Angela Spadola, Saveria Arciuolo, Damiano Valente, Michele Carlino, Angela Piermattei, Alessia Scaglione, Giulia Scambia, Giovanni Rindi, Guido Zannoni, Gian Franco Cancers (Basel) Article Background. Gynecological neuroendocrine neoplasms (NENs) are extremely rare, accounting for 1.2–2.4% of the NENs. The aim of this study was to test cervical NENs for novel markers of potential utility for differential diagnosis and target therapy. Methods. All cases of our center (n = 16) were retrieved and tested by immunohistochemistry (IHC) for 12 markers including markers of neuroendocrine differentiation (chromogranin A, synaptophysin, CD56), transcription factors (CDX2 and TTF1), proteins p40, p63, p16INK4a, and p53, somatostatin receptors subtypes (SST2-SST5) and the proliferation marker Ki67 (MIB1). Results. All cases were poorly differentiated neuroendocrine carcinomas (NECs), 10 small cell types (small cell–neuroendocrine carcinomas, SCNECs) and 6 large cell types (large cell–neuroendocrine carcinomas, LCNECs); in 3 cases a predominant associated adenocarcinoma component was observed. Neuroendocrine cancer cells expressed at least 2 of the 3 tested neuroendocrine markers; p16 was intensely expressed in 14 (87.5%) cases; SST5 in 11 (56.25%, score 2–3, in 9 cases); SST2 in 8 (50%, score 2–3 in 8), CDX2 in 8 (50%), TTF1 in 5 (31.25%), and p53 in 1 case (0.06%). P63 and p40 expressions were negative, with the exception of one case that showed moderate expression for p63. Conclusions. P40 is a more useful marker for the differential diagnosis compared to squamous cell carcinoma. Neither CDX2 nor TTF1 expression may help the differential diagnosis versus potential cervical metastasis. P16 expression may suggest a cervical origin of NEC; however, it must be always integrated by clinical and instrumental data. The expression of SST2 and SST5 could support a role for SSAs (Somatostatin Analogues) in the diagnosis and therapy of patients with cervical NECs. MDPI 2020-05-12 /pmc/articles/PMC7281076/ /pubmed/32408525 http://dx.doi.org/10.3390/cancers12051211 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Inzani, Frediano
Santoro, Angela
Angelico, Giuseppe
Feraco, Angela
Spadola, Saveria
Arciuolo, Damiano
Valente, Michele
Carlino, Angela
Piermattei, Alessia
Scaglione, Giulia
Scambia, Giovanni
Rindi, Guido
Zannoni, Gian Franco
Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title_full Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title_fullStr Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title_full_unstemmed Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title_short Neuroendocrine Carcinoma of the Uterine Cervix: A Clinicopathologic and Immunohistochemical Study with Focus on Novel Markers (Sst2–Sst5)
title_sort neuroendocrine carcinoma of the uterine cervix: a clinicopathologic and immunohistochemical study with focus on novel markers (sst2–sst5)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281076/
https://www.ncbi.nlm.nih.gov/pubmed/32408525
http://dx.doi.org/10.3390/cancers12051211
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