TY - JOUR
T1 - RB1 gene mutations are a distinct predictive factor in Merkel cell carcinoma
AU - Muto, Yusuke
AU - Ryo, Eijitsu
AU - Namikawa, Kenjiro
AU - Takahashi, Akira
AU - Ogata, Dai
AU - Fujimura, Taku
AU - Yatabe, Yasushi
AU - Aiba, Setsuya
AU - Yamazaki, Naoya
AU - Mori, Taisuke
N1 - Funding Information:
This work was supported in part by the National Cancer Center Research and Development Fund (grant no. 2020-J-3 to NY), JSPS KAKENHI (Grants-in-Aid for Scientific Research, grant no. 20K07383 to TM), and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan.
Publisher Copyright:
© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that tends to show local recurrence and metastasis. Typically, MCC is polyomavirus (MCPyV)-associated and cytokeratin 20 (CK20) positive. However, little is known about this tumor and its origins. Here, we aimed to determine the developmental origins of MCC and to identify prognostic clinicopathologic factors. Initial examinations revealed that CK20 and MCPyV expression (CK20+, MCPyV+ (60%); CK20+, MCPyV− (10%); CK20−, and MCPyV− (30%)) did not affect overall survival. With RB1 gene sequencing of FFPE specimens, which covered an entire exon, all RB1 mutation-positive cases showed positive regional lymph node and/or distant metastases (8/8 cases, 100%), whereas the frequency of the metastasis was statistically significantly lower in RB1 mutation-negative cases, (10/16 cases, 62%, P = 0.033). The results were also confirmed with immunohistochemistry, and either RB1 alterations, entire exon sequencing, or immunohistochemistry was associated with the metastasis (P = 0.007). RB1 alterations may be used to access the aggressive clinical course of MCC.
AB - Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that tends to show local recurrence and metastasis. Typically, MCC is polyomavirus (MCPyV)-associated and cytokeratin 20 (CK20) positive. However, little is known about this tumor and its origins. Here, we aimed to determine the developmental origins of MCC and to identify prognostic clinicopathologic factors. Initial examinations revealed that CK20 and MCPyV expression (CK20+, MCPyV+ (60%); CK20+, MCPyV− (10%); CK20−, and MCPyV− (30%)) did not affect overall survival. With RB1 gene sequencing of FFPE specimens, which covered an entire exon, all RB1 mutation-positive cases showed positive regional lymph node and/or distant metastases (8/8 cases, 100%), whereas the frequency of the metastasis was statistically significantly lower in RB1 mutation-negative cases, (10/16 cases, 62%, P = 0.033). The results were also confirmed with immunohistochemistry, and either RB1 alterations, entire exon sequencing, or immunohistochemistry was associated with the metastasis (P = 0.007). RB1 alterations may be used to access the aggressive clinical course of MCC.
KW - Merkel cell carcinoma
KW - RB1
KW - clinicopathological examination
UR - http://www.scopus.com/inward/record.url?scp=85102841979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102841979&partnerID=8YFLogxK
U2 - 10.1111/pin.13090
DO - 10.1111/pin.13090
M3 - Article
C2 - 33751708
AN - SCOPUS:85102841979
SN - 1320-5463
VL - 71
SP - 337
EP - 347
JO - Acta Pathologica Japonica
JF - Acta Pathologica Japonica
IS - 5
ER -