Genomic analysis of circulating tumor cells in adenosquamous carcinoma of the prostate: a case report

Junji Kitamura; Satoru Taguchi; Takatsugu Okegawa; Kazuki Honda; Toshihiko Kii; Yoshihiro Tomida; Ryuki Matsumoto; Naoki Ninomiya; Kazuki Masuda; Yu Nakamura; Tsuyoshi Yamaguchi; Manami Kinjo; Mitsuhiro Tambo; Aya Isomura; Akimasa Hayashi; Hiroshi Kamma; Eiji Higashihara; Junji Shibahara; Hiroshi Fukuhara

doi:10.1186/s12920-021-01068-w

Genomic analysis of circulating tumor cells in adenosquamous carcinoma of the prostate: a case report

BMC Med Genomics. 2021 Sep 3;14(1):217. doi: 10.1186/s12920-021-01068-w.

Authors

Junji Kitamura^#¹, Satoru Taguchi^#², Takatsugu Okegawa¹, Kazuki Honda¹, Toshihiko Kii¹, Yoshihiro Tomida¹, Ryuki Matsumoto¹, Naoki Ninomiya¹, Kazuki Masuda¹, Yu Nakamura¹, Tsuyoshi Yamaguchi¹, Manami Kinjo¹, Mitsuhiro Tambo¹, Aya Isomura³, Akimasa Hayashi³, Hiroshi Kamma³, Eiji Higashihara⁴, Junji Shibahara³, Hiroshi Fukuhara¹

Affiliations

¹ Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
² Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan. satorutaguchi33@gmail.com.
³ Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.
⁴ Department of ADPKD Research, Kyorin University School of Medicine, Tokyo, Japan.

^# Contributed equally.

Abstract

Background: Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP.

Case presentation: A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient's blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)⁺ CTCs, 14 CK^- CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes: PIK3CB, APC, CDKN2A, PTEN, BRCA2, RB1, TP53, and CDK12. Of 14 mutations, 9 (64%) were detected on CK^- CTCs and 5 (36%) were detected on CK⁺ CTCs.

Conclusions: This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.

Keywords: Adenosquamous carcinoma; Case report; Circulating tumor cell; Liquid biopsy; Prostate cancer.

MeSH terms

Neoplastic Cells, Circulating*