TY - JOUR
T1 - p16 in highly malignant esophageal carcinomas
T2 - the correlation with clinicopathological factors and human papillomavirus infection
AU - Ishida, Hirotaka
AU - Kasajima, Atsuko
AU - Fujishima, Fumiyoshi
AU - Akaishi, Ryujiro
AU - Ueki, Shunsuke
AU - Yamazaki, Yuto
AU - Onodera, Yoshiaki
AU - Gao, Xin
AU - Okamoto, Hiroshi
AU - Taniyama, Yusuke
AU - Kamei, Takashi
AU - Sasano, Hironobu
N1 - Funding Information:
The authors would like to acknowledge Dr. Yoichi Tanaka and Dr. Masafumi Kurosumi (Saitama Cancer Center, Saitama, Japan), Dr. Masahiro Chin and Dr. Akiko Nishida (Nihonkai General Hospital, Yamagata, Japan), Dr. Go Miyata and Dr. Tsutomu Sakuma (Iwate Prefectural Central Hospital, Iwate, Japan), Dr. Shunsuke Shibuya and Dr. Kazuyuki Ishida (Iwate Prefectural Isawa Hospital, Iwate, Japan), and Dr. Kenichi Yokota (Kesennuma City Hospital, Miyagi, Japan) for providing tissue samples and clinical data. We also thank Ms. Kazue Ise, Ms. Erina Iwabuchi, Ms. Yayoi Aoyama, Mr. Katsuhiko Ono, and Ms. Yasuko Furukawa (Tohoku University, Sendai, Japan); Dr. Naomi Oka, Dr. Junko Sakurada, and Dr. Hiroyoshi Suzuki (National Hospital Organization Sendai Medical Center, Sendai, Japan); and Dr. Ichiro Abe and Dr. Makiko Abe (Griffith University, Gold Coast, Australia) for their excellent technical and statistical support.
Funding Information:
Open Access funding provided by Projekt DEAL. This work was supported in part by the Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (JSPS KAKENHI Grant Number JP26460413) and funding provided by Alexander von Humboldt foundation (to A.K.). Acknowledgments
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/2
Y1 - 2021/2
N2 - p16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P < 0.001). HPV was detected in none of the p16-positive cases examined. Clinical outcome of the p16-positive high-grade squamous cell carcinomas was not different from that of the p16-negative counterparts (P = 0.687) but significantly better than those with the small-cell carcinomas (P = 0.023). p16 was therefore considered to be induced through an inactivation of the RB1 signaling pathway and not through HPV infection in highly malignant esophageal neoplasms. Nevertheless, patients’ clinical outcome of these neoplasms significantly differs; therefore, small-cell carcinomas have to be carefully differentiated from other neoplasms. In addition, p16 overexpression is not predictive of favorable clinical outcome in high-grade squamous cell carcinomas of the esophagus.
AB - p16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P < 0.001). HPV was detected in none of the p16-positive cases examined. Clinical outcome of the p16-positive high-grade squamous cell carcinomas was not different from that of the p16-negative counterparts (P = 0.687) but significantly better than those with the small-cell carcinomas (P = 0.023). p16 was therefore considered to be induced through an inactivation of the RB1 signaling pathway and not through HPV infection in highly malignant esophageal neoplasms. Nevertheless, patients’ clinical outcome of these neoplasms significantly differs; therefore, small-cell carcinomas have to be carefully differentiated from other neoplasms. In addition, p16 overexpression is not predictive of favorable clinical outcome in high-grade squamous cell carcinomas of the esophagus.
KW - Basaloid squamous cell carcinoma
KW - Esophagus
KW - Human papillomavirus
KW - Poorly differentiated squamous cell carcinoma
KW - Small-cell carcinoma
KW - p16
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UR - http://www.scopus.com/inward/citedby.url?scp=85086564086&partnerID=8YFLogxK
U2 - 10.1007/s00428-020-02865-x
DO - 10.1007/s00428-020-02865-x
M3 - Article
C2 - 32556556
AN - SCOPUS:85086564086
VL - 478
SP - 219
EP - 229
JO - Virchows Archiv - Abteilung A Pathologische Anatomie
JF - Virchows Archiv - Abteilung A Pathologische Anatomie
SN - 0945-6317
IS - 2
ER -