Immunohistochemical analysis of PD-L1 and tumor-infiltrating immune cells expression in the tumor microenvironment of primary signet ring cell carcinoma of the prostate

Abstract

Primary signet ring cell carcinoma (SRCC) of the prostate is a rare neoplasm. However, its potential tumorigenic mechanism, clinicopathological features, and prognostic outcome have not been systematically described. To determine the pathogenic mechanism, we detected distributions of programmed cell death-ligand 1 (PD-L1), programmed death 1 (PD-1), and cellular components in the tumor microenvironment, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (TAMs; CD163 and CD68), and tumor-associated fibroblasts (vimentin and alpha-smooth muscle actin [α-SMA]), in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma (PCa) by immunohistochemical staining. We found higher expression of PD-L1, CD163, and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores, indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate. For further analysis, we searched electronic journal databases and Surveillance, Epidemiology, and End Results (SEER) to identify 200 eligible patients including our four cases. According to Kaplan–Meier survival curve analysis, patients <68 years old, with radical prostatectomy (RP), Gleason score of 7–8, and lower clinical stage had longer overall survival (OS). Moreover, Cox multivariate analysis indicated that race (hazard ratio [HR] = 1.422), surgical approach (HR = 1.654), and Gleason score (HR = 2.162) were independent prognostic factors for OS. Therefore, primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs, which warrants further clinical investigation.

A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review

“…Additionally, symptoms related to metastases may appear [ 8 ]. The patients may have variable serum PSA values ranging from 0.19 ng/mL to 1990 ng/mL [ 2 ]. Radiological findings (multiparametric MRI, transurethral ultrasound) are not specific [ 38 ].…”

“…To establish the diagnosis of a primary prostatic SRCC, it is also essential to perform upper gastric endoscopy, colonoscopy, cystoscopy, and abdominal computed CT to exclude metastatic involvement of the prostate by tumors arising from the gastrointestinal tract, urinary bladder, or pancreas [ 2 ]. Since the therapeutic approach is different, it is crucial to distinguish between these entities [ 9 ].…”

“…In addition to the unclear data of Hashimoto et al [ 67 ], our present systematic literature review resulted in only one paper describing four prostatic SRCCs tested for PD-L1 ( Table 1 ) [ 2 ].…”

“…Data collection was study- and case-related. As only 1 paper (describing 4 cases) was finally included [ 2 ], no significant statistical analysis was performed; the details of the article were reported in the Section 4 .…”

“…SRCC was first reported in 1981. Around 200 cases have been described in the English literature since then [ 2 , 3 , 4 , 5 ]. Histologically, the signet ring morphology of the tumor cells is characterized by an intracytoplasmic vacuole that compresses the nucleus into a crescent shape, displacing it to the cell periphery [ 6 , 7 ].…”