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Page 460 Julka et al. J Transl Genet Genom 2020;4:455-63 I http://dx.doi.org/10.20517/jtgg.2020.46

In view of response to chemotherapy and hormonal treatment, further IHC evaluation of tumor tissue was
performed to study the expression profiles of GnRHR, androgen receptor (AR) and immune checkpoint
marker PD-L1. Tumor tissue was sectioned at 4 µm and stained with hematoxylin/eosin, which revealed
prostatic adenocarcinoma [Figure 4A]. Initial baseline IHC evaluation indicated the case to be AR-negative
with very low expression of PD-L1 but positive for GnRHR [Figure 4B]. To understand the possible
role of GnRHR, we first tested the receptor expression post-treatment with its antagonist degarelix on
the CANscript platform. The results indicated that treatment with degarelix decreased the expression of
GnRHR-positive cells [Figure 4C]. This retrospective corroboration based on post-treatment response
evaluation further confirmed our clinical diagnosis of prostate cancer despite the diagnostic dilemma.
Furthermore, bladder cancer does not have these receptors, and prostate cancers are known to be hormone
responsive, so the prostate origin of the tumor was further corroborated.

DISCUSSION
ACC of the prostate is a rare and uncommon malignancy with no well-defined management strategy for the
[21]
patients with advanced and metastatic disease. ACC of the prostate was first described by Frankel et al.
[21]
in 1974. Frankel et al. reported a 3-year asymptomatic period for a patient with transurethral resection of
[13]
the tumor. Iczkowski et al. (2003) reported clinicopathological findings of ACC of the prostate in 19 cases.
Of the 19 patients, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and
the rest had no treatment after diagnosis. At a follow-up of 0.3 to 11.8 years, 2 patients died of cancer,
[15]
3 remained alive with cancer, and 10 had no evidence of cancer. Schmid et al. (2002) reported a local
recurrence in a 44-year-old patient after 7 years of radical prostatectomy and adjuvant radiotherapy, whot
was treated with external beam irradiation. After an extended follow-up of more than 9 years, the patient
[10]
remained asymptomatic with stable disease. McKenney et al. (2004) reported a clinicopathological study
of 23 cases of basal cell proliferations of the prostate other than usual basal cell hyperplasia, including four
carcinomas. Of the 4 carcinoma cases, 1 patient with ACC of the prostate died with extensive metastasis,
and the other 3 did not progress at a mean follow-up of 7 years. Unlike these studies that reported ACC
of the prostate to be a biologically indolent disease with relatively low risk of distant metastasis, our case
demonstrated distant metastasis within 3 weeks of surgical procedure. This not only led to the diagnostic
dilemma in the present case but also suggested that ACC of the prostate may be an aggressive disease in
some cases. The age at presentation in our case was also higher than the age range reported in previous
[13]
studies . The normal PSA level in our study was consistent with previous reports [14,15] .
To the best of our knowledge, only two cases of ACC of the prostate have been reported from India to date.
In one of the reports, a 62-year-old man underwent bilateral orchidectomy after diagnosis followed by
[22]
hormonal treatment with stable disease in a limited follow-up period of 6 months . In the second report,
a 68-year-old underwent channel transurethral resection of prostate and bilateral orchidectomy with no
new metastasis at a follow-up of 3 years . We report the first case of ACC of the prostate treated with
[23]
paclitaxel and carboplatin-based combination chemotherapy regime along with ADT using CANscript
test. It is worthwhile to note that paclitaxel and carboplatin as a combination chemotherapy was never
a first choice either for bladder or prostate cancer. The CANscript ex vivo assay lacks the pituitary-testes
axis therefore, the luteinizing hormone-releasing hormone (LHRH) antagonist, degarelix is possibly
acting directly on the tumor cells. There are few preclinical reports where prostate cancer cell lines have
shown response to degarelix . The scientific explanation for this is based on the observation that LHRH
[24]
receptors are present on the surface of the tumor cells thereby contributing to an autocrine response. It is
possible the degarelix acts directly on prostate cell growth, as these cells express GnRHR that affects non-
tumorigenic, hyperplasia-type and tumorigenic cells. This case demonstrates that the CANscript test can
assist in resolving the diagnostic dilemma in a rare case of ACC of the prostate. Further, the stable disease
along with necrosis achieved in this case establishes the clinical utility of CANscript test in determining the
positive prediction of treatment response in rare tumors.