Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Hum Pathol. 2020 Jul;101:70-79. doi: 10.1016/j.humpath.2020.04.014. Epub 2020 May 7.
Small-cell neuroendocrine carcinoma (SCNC) of the prostate is an aggressive subtype with frequent TP53 mutation and RB1 inactivation; however, the molecular phenotype remains an area of investigation. Here, we compared telomere lengths in prostatic SCNC and usual-type prostatic adenocarcinoma (AdCa). We studied 32 cases of prostatic SCNC (including 11 cases with concurrent AdCa) and 347 cases of usual-type AdCa on tissue microarrays. Telomere lengths in tumor cells were qualitatively compared with those in normal cells using a telomere-specific fluorescence in situ hybridization assay. ERG, PTEN, and TP53 status were assessed in a proportion of cases using genetically validated immunohistochemistry protocols. Clinicopathological and molecular characteristics of cases were compared between the telomere groups using the chi-square test.A significantly higher proportion of prostatic SCNC cases (50%, 16/32) showed normal/long telomeres compared with AdCa cases (11%, 39/347; P < 0.0001). In 82% (9/11) of cases with concurrent SCNC and AdCa, the paired components were concordant for telomere length status. Among AdCa cases, the proportion of cases with normal/long telomeres significantly increased with increasing tumor grade group (P = 0.01) and pathologic stage (P = 0.02). Cases with normal/long telomeres were more likely to be ERG positive (P = 0.04) and to have TP53 missense mutation (P = 0.01) than cases with short telomeres.Normal or long telomere lengths are significantly more common in prostatic SCNC than in AdCa and are similar between concurrent SCNC and AdCa tumors, supporting a common origin. Among AdCa cases, longer telomere lengths are significantly associated with high-risk pathologic and molecular features.
前列腺小细胞神经内分泌癌（SCNC）是一种侵袭性亚型，常伴有 TP53 突变和 RB1 失活；然而，其分子表型仍是研究领域。在此，我们比较了前列腺 SCNC 和常见型前列腺腺癌（AdCa）的端粒长度。我们在组织微阵列上研究了 32 例前列腺 SCNC（包括 11 例伴有同时性 AdCa）和 347 例常见型 AdCa。使用端粒特异性荧光原位杂交检测，定性比较肿瘤细胞中端粒长度与正常细胞中的端粒长度。在部分病例中，使用经过基因验证的免疫组织化学方案评估 ERG、PTEN 和 TP53 状态。使用卡方检验比较端粒组之间的病例临床病理和分子特征。与 AdCa 病例（11%，39/347；P<0.0001）相比，前列腺 SCNC 病例（50%，16/32）中表现出正常/长端粒的比例显著更高。在 82%（9/11）的同时性 SCNC 和 AdCa 病例中，配对成分的端粒长度状态一致。在 AdCa 病例中，正常/长端粒的比例随着肿瘤分级组（P=0.01）和病理分期（P=0.02）的增加而显著增加。具有正常/长端粒的病例更可能为 ERG 阳性（P=0.04），并且具有 TP53 错义突变（P=0.01），而具有短端粒的病例则不然。与 AdCa 相比，前列腺 SCNC 中正常或长端粒长度的比例显著更高，并且在同时性 SCNC 和 AdCa 肿瘤中相似，支持共同起源。在 AdCa 病例中，更长的端粒长度与高风险的病理和分子特征显著相关。
