Neuroendocrine Small-cell Cancer Research Articles

PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity.

Our study provides functional evidence that metabolic reprogramming can directly impact cancer phenotypes and establishes PGC-1α-induced mitochondrial metabolism as a driver of SCNC progression and lineage determination. These mechanistic insights reveal common metabolic vulnerabilities across SCNCs originating from multiple tissues, opening new avenues for pan-SCN cancer therapeutic strategies.

Clinical case: multimix profiling of a tissue sample of small cell neuroendocrine lung cancer in order to clarify the diagnosis and select options for antitumor therapy

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Diagnostic Role and Prognostic Impact of PSAP Immunohistochemistry: A Tissue Microarray Study on 31,358 Cancer Tissues.

Prostate-specific acid phosphatase (PSAP) is a marker for prostate cancer. To assess the specificity and prognostic impact of PSAP, 14,137 samples from 127 different tumor (sub)types, 17,747 prostate cancers, and 76 different normal tissue types were analyzed via immunohistochemistry in a tissue microarray format. In normal tissues, PSAP staining was limited to the prostate epithelial cells. In prostate cancers, PSAP was seen in 100% of Gleason 3 + 3, 95.5% of Gleason 4 + 4, 93.8% of recurrent cancer under androgen deprivation therapy, 91.0% of Gleason 5 + 5, and 31.2% of small cell neuroendocrine cancer. In non-prostatic tumors, PSAP immunostaining was only found in 3.2% of pancreatic neuroendocrine tumors and in 0.8% of diffuse-type gastric adenocarcinomas. In prostate cancer, reduced PSAP staining was strongly linked to an advanced pT stage, a high classical and quantitative Gleason score, lymph node metastasis, high pre-operative PSA levels, early PSA recurrence (p < 0.0001 each), high androgen receptor expression, and TMPRSS2:ERG fusions. A low level of PSAP expression was linked to PSA recurrence independent of pre- and postoperative prognostic markers in ERG-negative cancers. Positive PSAP immunostaining is highly specific for prostate cancer. Reduced PSAP expression is associated with aggressive prostate cancers. These findings make PSAP a candidate marker for prognostic multiparameter panels in ERG-negative prostate cancers.

Clinical observation of small cell neuroendocrine cancer of the tracheal bifurcation zone, with metastasis to the bone marrow, liver, spleen

Aim. Demonstration of a clinical case of a patient with small cell neuroendocrine cancer of the tracheal bifurcation zone, with metastases to the bone marrow, liver, spleen.Materials and methods. A brief review of the literature on the diagnosis of neuroendocrine tumors of the lungs and bronchi is presented, and a clinical observation of small cell neuroendocrine cancer of the tracheal bifurcation zone with metastases to the bone marrow, liver and spleen from the personal practice of the authors is presented.Results. The clinical picture of this patient was dominated by “hematological” manifestations: severe thrombocytopenia and hemorrhagic syndrome, anemia, due to which differential diagnosis with a systemic blood disease was initially carried out. There was no pain syndrome in the bones characteristic of metastatic lesions. Histological examination of the bronchial tumor biopsy and bone marrow trephine biopsy with immunohistochemical examination (IHC) helped in making the diagnosis. In both cases, IHC revealed tumor cells with the same phenotype.Conclusion. Metastasis of tumors to the bone marrow can proceed without characteristic ossalgia and manifest itself only in hematological syndromes (changes in blood tests). Cytological and histological examination of the bone marrow, with IHC, helps in the diagnosis.

Development of an improved diagnostic nomogram for preoperative prediction of small cell neuroendocrine cancer of the cervix.

Accurate preoperative diagnosis of small cell neuroendocrine cancer of the cervix (SCNECC) is crucial for establishing the best treatment plan. This study aimed to develop an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information. A total of 105 pathologically confirmed cervical cancer patients (35 SCNECC, 70 non-SCNECC) from multiple centres with complete clinical and MR records were included. Whole lesion histogram analysis of the ADC was performed. Multivariate logistic regression analysis was used to develop diagnostic models based on clinical, morphological, and histogram data. The predictive performance in terms of discrimination, calibration, and clinical usefulness of the different models was assessed. A nomogram for preoperatively discriminating SCNECC was developed from the combined model. In preoperative SCNECC diagnosis, the combined model, which had a diagnostic AUC (area under the curve) of 0.937 (95% CI: 0.887-0.987), outperformed the clinical-morphological model, which had an AUC of 0.869 (CI: 0.788-0.949), and the histogram model, which had an AUC of 0.872 (CI: 0.792-0.951). The calibration curve and decision curve analyses suggest that the combined model achieved good fitting and clinical utility. Non-invasive preoperative diagnosis of SCNECC can be achieved with high accuracy by integrating clinical, MR morphological, and ADC histogram features. The nomogram derived from the combined model can provide an easy-to-use clinical preoperative diagnostic tool for SCNECC. It is clear that the therapeutic strategies for SCNECC are different from those for other pathological types of cervical cancer according to V 1.2021 of the NCCN clinical practice guidelines in oncology for cervical cancer. This research developed an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information.

Phase 1a/1b study of FOR46, an antibody drug conjugate (ADC), targeting CD46 in metastatic castration-resistant prostate cancer (mCRPC).

3001 Background: FOR46, a fully human antibody (ab) conjugated to monomethyl auristatin E (MMAE), targets a tumor selective epitope of CD46, which is highly expressed in mCRPC and treatment-emergent small cell neuroendocrine cancer (t-SCNC). CD46 is enriched in tumor cells upon treatment with androgen signaling inhibitors (ASI). Following dose escalation (Phase 1a), dose expansion was undertaken in 2 cohorts (Phase 1b): 1) Pts with de novo or t-SCNC and 2) pts with mCRPC without a t-SCNC component. Pts with adenocarcinoma enrolled in dose escalation and expansion are included in this analysis. Methods: Eligible pts had mCRPC, with progression on at least 1 ASI, with no prior chemotherapy for CRPC. Phase 1a pts received FOR46 0.1-3.0 mg/kg IV Q3 weeks (wks). The primary objectives in phase 1a were to assess adverse effects (AEs) and select the phase 1b dose; and in phase 1b to assess efficacy. For phase 1b, tumor biopsy in the CRPC setting for assignment to the 2 cohorts was required. CD46 expression was not required for inclusion in the expansion cohort, but was evaluated using a non-epitope specific CD46 polyclonal ab. Histology and CD46 expression were centrally reviewed. Results: Thirty-three pts were enrolled in phase 1a and 10 in phase 1b (including 6 treated in ph1a at the expansion dose or higher). Overall, 36 pts were treated at doses &gt; 1.2 mg/kg. Following excess toxicity in pts with body mass indices &gt; 30 (3 of 3 with Gr 4 neutropenia and 1 of 3 with Gr 3 fatigue at 2.4 mg/kg), further dosing was calculated using adjusted body weight (AJBW) rather than actual weight, allowing escalation to 3.0 mg/kg. The 2.7 mg/kg dose by AJBW was determined to be the MTD and phase 1b dose. The most common AEs at the 2.7 mg/kg dose were neutropenia (77% Gr 3 or 4), infusion reactions (37%, all &lt; Gr 2), fatigue (31%, all &lt; Gr 2) and peripheral neuropathy (24%, all &lt; Gr 2)). Fourteen of 31 evaluable pts (45.2%) at &gt; 1.2 mg/kg achieved a PSA50 response with 10 (32.3%) confirmed. Five pts were not evaluable for PSA response; 3 had no post-baseline PSA and 2 had baseline PSA &lt; 1 ng/mL. The median duration of confirmed PSA50 response is &gt;16 wks (range 6-48+ wks, with 4 ongoing at 12, 24, 25 and 48 wks). 18 pts had measurable lesions; 8 of 18 (44.4%) had tumor regression, with 4 (22.2%) confirmed partial responses (PR). The median duration of response is &gt; 14 wks (range 9 -31+ weeks with 2 ongoing at 13 and 31 wks). Eight pts were evaluable for CD46 expression with a median H-score of 245 (range 0-300). Two pts with PRs had H-scores of 15 and 300; 4 with confirmed PSA50 had H-scores of 10, 15, 40 and 300. Conclusions: FOR46, a novel ADC targeting CD46, demonstrates clinical activity in mCRPC pts, with an acceptable safety profile, similar to other MMAE-containing ADCs. FOR46 merits further investigation in pts with mCRPC, alone and in combination with agents that enhance CD46 expression. Clinical trial information: NCT03575819.

Clinicopathological Analysis of Neuroendocrine Carcinoma of the Uterine Cervix: A Single-Institution Retrospective Review of 9 Cases.

Aim To evaluate the clinicopathological features affecting the recurrence and survival of 9 cases of neuroendocrine cancer of the cervix. Method We retrospectively analyzed 9 cervical neuroendocrine cancer cases identified among 453 cervical cancer patients between 2004 and 2021 at Akdeniz University Gynecological Oncology Outpatient Clinic. Kaplan–Meier survival analysis was used for progression-free survival (PFS) and overall survival (OS). Mathematical functions of mean, standard deviation, median, Min–Max values, and frequencies were used for descriptive statistics. The categorical data were expressed in numbers and percentages (%). Results Nine patients with neuroendocrine histological subtype were selected out of 453 patients diagnosed with cervical cancer (1.98%). The average overall survival time of the patients was 26 months. The 5-year survival rate was 53.3%, while the PFS was 62.5%. The most common subtype was small cell neuroendocrine cancer. Tumours were mostly locally advanced at the time of diagnosis. 3 patients' stage was 1b2, while 4 patients were 2b, 1 patient was 3c2r, and 1 patient was 4b. All tumours showed the immunohistochemical staining properties of neuroendocrine cancer. The main treatment modality applied to our patients was surgery + adjuvant CRT. The most used chemotherapeutic agents were cisplatin/carboplatin and etoposide. Recurrence was found in 3 cases, including 5 deaths. Conclusion Neuroendocrine tumour of the cervix is a rare subtype with a poor prognosis. Unfortunately, there is not yet a standard treatment protocol due to the limited number of comparative studies of surgery, chemotherapy, and radiotherapy based treatment schemes.

Abstract 678: Exceptional response to PD-L1 inhibitor after radiation therapy in a patient with small cell neuroendocrine tumor of the prostate gland refractory to combination treatment with PD-1 and CTLA-4 inhibitors

Abstract Background: Immune checkpoint inhibitor (ICI) treatment became the new treatment paradigm of a wide spectrum of cancers in the last decade. However, overcoming unresponsiveness to ICI remains an important high unmet need in the field of immuno-oncology. It is unclear whether another ICI can be an effective treatment option in patients with tumors refractory to combinatorial immunotherapy. Here we describe a case in whom a significant response to a PD-L1 inhibitor was demonstrated when used concurrently with radiation therapy. Notably, this patient was found to be unresponsive to the combined ICI treatment of PD-1 and CTLA-4 inhibitors. Case Presentation: A 42 y.o. male patient who presented with urinary frequency and hematospermia was diagnosed with stage IV small cell neuroendocrine cancer of prostate gland with osseous metastasis. He was treated with cisplatin plus etoposide for 4 cycles and was subsequently treated with topotecan for 4 cycles given progression of disease (PD). He was given the combination of ipilimumab and nivolumab after another PD. Treatment was discontinued 5 months later due to a lack of response. Two months later, the patient received radiation therapy: 3000 cGy to the prostate and lower pelvis and palliative radiation therapy to the left femur. The patient subsequently underwent multiple lines of treatment with no satisfactory response. Follow up imaging test was concerning for progression with new liver and lung lesions. The treatment was switched to atezolizumab and nab-paclitaxel combination regimen. Concurrently, the patient had stereotactic ablative radiotherapy (4000 cGy) to pelvic region, paraspinal region and para-aortic LNs. Repeated imaging test after two months of the treatment showed an increase in pulmonary nodule size and the treatment was continued despite PD. The repeated scan after 6 weeks revealed an exceptional response that was close to resolution of the metastasized lesion in the liver and significant decrease in size of pulmonary metastatic lesions. Conclusion:This case illustrates the abscopal effect of targeted radiation treatment when coupled with immunotherapy. Exceptional responses seen in non-radiated lesions including lungs and liver after radiation to pelvic lymph nodes while on PD-L1 inhibitors corroborates the concept of synergistic effect of radiation and immunotherapy. Intriguingly, this concurrent treatment approach maximizing the abscopal effect was effective in this case where combinatorial immunotherapy with nivolumab and ipilimumab was ineffective. Future clinical trials are warranted to validate these findings in a more systematic fashion. Citation Format: Leeseul Kim, William Cheng, Yeun Ho Lee, Myungwoo Nam, Won Kyung Hur, Jin Young Hwang, Yoonhee Choi, William H Bae, Cyra Y. Kang, Heayoon Shauna Cho, Emma Yu, Chan Mi Jung, Eugene Kim, Christmann Low, Young Kwang Chae. Exceptional response to PD-L1 inhibitor after radiation therapy in a patient with small cell neuroendocrine tumor of the prostate gland refractory to combination treatment with PD-1 and CTLA-4 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 678.

A RARE HISTOLOGICAL FINDING AFTER PANCREATICODUODENECTOMY

In this paper, we describe the case of successful surgical treatment of a rare combination of three malignant tumors of the major duodenal papilla in one patient. A 59-year-old woman presented with abdominal pain, fever, nausea, vomiting, weight loss and obstructive jaundice. After routine examination, the patient with suspected cancer of the major duodenal papilla underwent pylorus-sparing pancreatoduodenal resection. Final histology revealed a rare collision of three types of cancer in the major duodenal papilla invading the pancreatic head: moderately-differentiated adenocarcinoma (30 %), moderately differentiated squamous cell carcinoma (20 %) and poorly differentiated small cell neuroendocrine cancer (50 %), surgical resection margins were intact. Immunohistochemical analysis revealed positivity for synaptophysin, chromogranin A and cytokeratin 5/6. The tumor diameter of 2 cm and the absence of signs of locoregional spread allowed the process to be staged as T2N0M0, so the patient did not receive any adjuvant treatment. Follow-up CT performed 6 months later showed two lesions in the liver, and biopsy of one of them was performed. Metastasis of neuroendocrine cancer was histologically and immunohistochemically verified. She started first-line chemotherapy with etoposide + cisplatin.

Feasibility study of gallium-68 citrate PET as a bone-tropic imaging biomarker in mCRPC.

31 Background: Transferrin receptor (TFRC) expression is controlled by the PI3K and MYC signaling pathways, which are frequently dysregulated in prostate cancer (PC). Gallium-68 citrate (68Ga-citrate) is an iron biomimetic, which can be used to image PC in a TFRC dependent fashion. We performed a single-center pilot imaging study to investigate the use of 68Ga-citrate PET in patients with metastatic castration-resistant PC (mCRPC). Methods: Following written informed consent, mCRPC patients were prospectively enrolled and underwent 68Ga-citrate PET imaging. Optional metastatic tumor biopsies were undertaken at the time of imaging. Results: 34 mCRPC patients underwent 68Ga-citrate PET imaging. The median age was 67.5 years old. Median duration of castration resistance was 17.5 months; 14.7% of patients were post-docetaxel. Median serum PSA was 35.2 ng/dL. A total of 483 lesions were detected on conventional imaging (CT, 99mTc-HDP) or 68Ga-citrate PET, including 420 osseous and 63 soft tissue (nodal and visceral) lesions (Table). 67.3% of all lesions were detected on 68Ga-citrate PET, including 74.5% of all osseous lesions but only 19.0% of all soft tissue lesions (p&lt;0.0001). Eight (1.7%) lesions were detected on 68Ga-citrate PET imaging only. Per-lesion average SUVmax (SUVmax,avg) was 6.7. Metastatic biopsies of PET avid lesions were performed in 20 patients (59%); adenocarcinoma histology was confirmed in 14 (70%) cases, treatment-emergent small cell neuroendocrine cancer (t-SCNC) in 6 (30%). There was no significant difference in SUVmax,avg between patients with adenocarcinoma or t-SCNC (SUVmax,avg 7.3 vs 7.6, respectively; Table). Serial 68Ga-citrate PET perfomed in a patient with biopsy-confirmed t-SCNC after 2 cycles of carboplatin/cabazitaxel demonstrated an early metabolic response (28.5% decrease in average SUVmax) confirmed on subsequent conventional imaging. Conclusions: 68Ga-citrate PET detects mCRPC bone metastases in patients with biopsy-proven prostatic adenocarcinoma or t-SCNC, distinguishing it from lineage dependent agents such as PSMA tracers. Detection of an early metabolic response in the bone of a treated t-SCNC patient was observed. Further prospective studies are ongoing coupling serial Ga-citrate PET with investigational agents targeting the MYC signaling pathway. Clinical trial information: NCT02391025. [Table: see text]

N‑Myc induces the tumor progression of prostate cancer by regulating FSCN1.

The oncoprotein N‑Myc has a carcinogenic effect in numerous types of cancer, and it can cause castration resistance in prostate cancer (PCa), and leads to the development of small cell neuroendocrine cancer by regulating multiple target genes. Immunohistochemical staining, RT‑qPCR, western blotting, wound healing and CCK‑8 assays were used to detect the expression of N‑Myc and FSCN1 as well as AR and CgA at the human level and cell level. The immunohistochemical results revealed that the protein levels of N‑Myc proto‑oncogene protein (N‑Myc) and fascin (FSCN1) in PCa were significantly higher than that of hyperplastic tissues (P<0.05), and there was a weak correlation between them (P=0.002). Invitro, N‑Myc and FSCN1 were overexpressed in LNCaP and C4‑2 cell lines. The results revealed the promoting effect of N‑Myc and FSCN1 on malignant progression of PCa. In addition, the endogenous FSCN1 was knocked down in the C4‑2 cell line, and the results revealed that the silencing of FSCN1 enhanced the expression of N‑Myc and weakened the expression of the neuroendocrine marker CgA. Therefore, the present findings indicated that N‑Myc may promote the malignant process of PCa by regulating FSCN1 and FSCN1 may have a reverse regulatory effect on N‑Myc.

Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission

BackgroundPoorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood.Case presentationAt our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years.The patient’s medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing.The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%.ConclusionsFor the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.

SAT-148 Ectopic ACTH Secretion Has Varied Presentation and Requires Individualized Treatment - One Size Does Not Fit All

Ectopic ACTH secretion (EAS) presents in myriad ways. We present five cases of EAS to highlight similarities and differences in presentation and treatment. The first woman with known metastatic lung neuroendocrine tumour (NET) for two years presented with facial fullness, proximal weakness, worsening hypertension and hypokalaemia. Random cortisol of 2742nmol/L (99.39mcg/dL), with adrenocorticotrophic hormone (ACTH) of 201ng/L (5-50), was in keeping with EAS. She received medical treatment followed by bilateral adrenalectomy with EAS resolution and development of adrenal insufficiency. She is doing well. The second woman with proximal weakness was evaluated by neurologists. All neurological tests were normal but facial fullness and easy bruising was noted. Random cortisol was 875nmol/L (31.71mcg/dL) and ACTH was 90 ng/L. Imaging revealed metastatic liver disease with unknown primary and biopsy confirmed NET. Cortisol rose despite medical treatment and she died within fifteen months. The third woman with significant smoking history presented with haemoptysis and breathlessness. A right lung mass was suspected on chest X-ray and confirmed with CT. Endobronchial ultrasound-guided biopsy revealed small cell lung cancer (SCLC). She developed generalised weakness and severe hypokalaemia. Random cortisol of 1645nmol/L (59.63mcg/dL) with ACTH of 282ng/L suggested EAS. Despite medical treatment, she died within two weeks. The fourth woman presented with confusion, hypertension and severe hypokalaemia. Morning cortisol of 8557nmol/L (310.19mcg/dL) and random ACTH of 73ng/L were suggestive of EAS. CT demonstrated left lung mass with widespread metastases. She deteriorated and died within 2 weeks. Our only man had incidentally discovered metastatic liver lesions on ultrasound. Further imaging revealed prostatic mass and biopsy showed small cell neuroendocrine cancer. He presented with severe hypokalaemia. Random cortisol was 1065nmol/L (38.61mcg/dL) and ACTH was 188ng/L. He was commenced on medical treatment but declined rapidly and died.All our patients had profound hypokalaemia and metastatic disease at presentation. Many patients do not exhibit classical cushingoid features as EAS tends to develop acutely and underlying malignancy drives weight loss. A high index of suspicion is required to make a diagnosis. EAS should be considered in patients with proximal myopathy, pigmentation, resistant or severe hypokalaemia or hypertension and known or suspected malignancy. Early and quick control of cortisol excess is essential to minimise cardiometabolic abnormalities, severe infections and thromboembolic complications. Prognosis depends upon age, frailty, comorbidity, nature of neoplasm and extent of hypercortisolaemia. Adrenolytics with or without bilateral adrenalectomy, reduction in tumour burden and management of complications are the mainstay of treatment.

MP16-12 METHYLATION CAN REGULATE THE EXPRESSION OF PD-L1 IN SMALL CELL PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP16)1 Apr 2020MP16-12 METHYLATION CAN REGULATE THE EXPRESSION OF PD-L1 IN SMALL CELL PROSTATE CANCER Yi Sun*, Qiang Wei, Jiaoti Huang, and Lu Yang Yi Sun*Yi Sun* More articles by this author , Qiang WeiQiang Wei More articles by this author , Jiaoti HuangJiaoti Huang More articles by this author , and Lu YangLu Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000841.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: As a broad generality, programmed death-ligand 1 (PD-L1)–positive tumors tend to have a higher rate of objective response to PD-1/PD-L1 blockade, and PD-L1 expression remains an important clinically validated predictive biomarker for response, in addition, according to some published paper, the expression of PD-L1 is much higher in small cells neuroendocrine prostate cancer. So we focus on the mechanism of this phenomena. METHODS: We collect the human tissue samples and performed the Immunohistochemistry (IHC) stain to test the expression of PD-L1, and also use the Interferon-g (IFN-g) to treat some cells lines test the expression of PD-L1. Moreover, we also test the expression of PD-L1 in xenograft mice model treated by IFN-g. And then we test the expression and the activation of the whole IFN respond pass-way in human tissue samples, mice tumor samples and cell lines. To test the effect of JAK/STAT pass-way on this process, we block the JAK/STAT pass-way and then test the IFN respond again. And then we test the impact of methylation on the expression of JAK1 also the INF respond. RESULTS: The comprehensive evaluation of PD-L1 expression in prostate cancer showed that PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in Small Cell Neuroendocrine (SCNE) prostate cancer. Similar results could be found in Small Cell Neuroendocrine Cancer (SCNC) cells and the SCNC mice model under the stimulation of IFN-g. Block the JAK1/STAT1 pass-way could drastically inhibit this process. The expression of JAK1 and this whole process also suppressed by demethylation. CONCLUSIONS: This study demonstrated that PD-L1 expression is much higher in a small cell prostate cancer. And the reason behind this phenomenon is the JAK/STAT pass-way regulated by methylation. Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81300627, 81702536, 81770756 and 81200551), This study was supported by the National key research and development program of China (Grant No. SQ2017YFSF090096), the Prostate Cancer Foundation Young Investigator Award 2013, Foundation of Science &Technology Department of Sichuan Province (Grant No. 2015SZ0230, 2013SZ0006 and 2013SZ0093), Programs from Science and Technology Department of Sichuan Province (Grant No. 2018JY0089 and 2017HH0063), Young Investigator Award of Sichuan University 2017, and the Scientific Research Project of Health Department of Sichuan Province (No. 120203). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e219-e220 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Sun* More articles by this author Qiang Wei More articles by this author Jiaoti Huang More articles by this author Lu Yang More articles by this author Expand All Advertisement PDF downloadLoading ...

Neuroendocrine carcinoma of the prostate (review of the literature)

Neuroendocrine neoplasia (NEC) of the prostate gland is a rather rare extrapulmonary neuroendocrine carcinoma and makes up only 0.5 to 1% of all malignant neoplasms of this localization. NEC of the prostate gland is a tumor of epithelial origin, histologically and immunohistochemically identical to analogues in the lungs and digestive system. When stained with hemotoxylin-eosin, neuroendocrine cells cannot always be visualized; they are best recognized by the immunohistochemical method of investigation using specific markers. Currently, a number of neuroendocrine markers are used, the expression of which may indicate a neuroendocrine nature. Androgen neuroendocrine cells themselves are independent and do not cause an increase in the concentration of prostate-specific antigen. Prostate NECs are represented by some histological forms according to WHO classification (2015): 1. Adenocarcinoma with focal neuroendocrine differentiation. 2. Well-differentiated neuroendocrine tumor. 3. Small cell neuroendocrine cancer is a high - grade tumor with high malignant potential. 4. Large cell neuroendocrine cancer is a high - grade tumor. Due to the rarity of NEC of the prostate, a specific algorithm for diagnosis and treatment has not been developed, as a rule, they are similar to methods of other malignant forms of prostate cancer and neuroendocrine tumors.

One Case of Interventional Chemoembolization Treatment of Small Cell Neuroendocrine Cervical Cancer

Small cell neuroendocrine cervical cancer (SCNEC) is some kind of rare malignant cancer of the cervix area. In 1997, according to the research of International Cancer Institute and the American Association of Pathology, the pancreatic endocrine tumors can be sorted into four types by the morphological similarity compared with tumors of the same type in the lung: typical carcinoid, non-typical carcinoid, large cell neuroendocrine cancer, and small cell neuroendocrine cancer, in which the last one is the most previaling. The SCNEC recurs much more often and its distant metastasis is more common in the lungs, brain and liver[1][2]. It characterizes low incidence and few cases, and a retrospective study is commonly used. Without clinical experience, there have been no fair treatment so far. A patient diagnosed as SCNEC A2 period was treated in our hospital, and uterine artery embolization chemotherapy, a new treatment, was taken to her. Consequently, the treatment worked, creating significant surgical conditions for her. Moreover, postoperative examination showed obvious effect of this treatment. The case report is as follows:

Lenalidomide as potential treatment in small cell neuroendocrine lung cancer with del 5q

Lung cancer is a leading cause of cancer deaths world-wide, with the carcinogens in tobacco smoke playing a major etiologic role.

Triple synchronous primary lung cancer: a case report and review of the literature

BackgroundMultiple primary lung cancer may present in synchronous or metachronous form. Synchronous multiple primary lung cancer is defined as multiple lung lesions that develop at the same time, whereas metachronous multiple primary lung cancer describes multiple lung lesions that develop at different times, typically following treatment of the primary lung cancer. Patients with previously treated lung cancer are at risk for developing metachronous lung cancer, but with the success of computed tomography and positron emission tomography, the ability to detect both synchronous and metachronous lung cancer has increased.Case presentationWe present a case of a 63-year-old Hispanic man who came to our hospital for evaluation of chest pain, dry cough, and weight loss. He had recently been diagnosed with adenocarcinoma in the right upper lobe, with a poorly differentiated carcinoma favoring squamous cell cancer based on bronchoalveolar lavage of the right lower lobe for which treatment was started. Later, bronchoscopy incidentally revealed the patient to have an endobronchial lesion that turned out to be mixed small and large cell neuroendocrine lung cancer. Our patient had triple synchronous primary lung cancers that histologically were variant primary cancers.ConclusionsTriple synchronous primary lung cancer management continues to be a challenge. Our patient’s case suggests that multiple primary lung cancers may still occur at a greater rate than can be detected by high-resolution computed tomography.

Role of Radical Surgery in Early Stages of Vaginal Cancer-Our Experience.

The objective of our present study was to evaluate the efficacy of radical vaginectomy with or without radical hysterectomy in patients with International Federation of Gynecology and Obstetrics stage I and II vaginal cancers. A retrospective study was carried out on 11 patients aged 35 to 78 years. All the patients underwent radical surgery for vaginal cancer from April 2010 till June 2015. Kaplan-Meier analyses were used to calculate the disease-free survival and overall survival at 12 months. The mean age of patients was 53.2 years. Ten patients were with International Federation of Gynecology and Obstetrics stage I, whereas one had stage II vaginal cancer. The histology was squamous cell cancer in 9 patients and small cell neuroendocrine cancer in 2 patients. The lesion was confined to the upper two third of the vagina in 8 cases, and the lower one third was involved in 3 cases. All the patients underwent radical surgery. Lymph node dissection was done in 9 patients out of whom lymph nodes were positive in 3 patients. Two patients had positive margins. Adjuvant treatment was given to patients with positive margins or positive nodes. Five patients did not require any adjuvant treatment, and 1 patient defaulted adjuvant treatment. One patient developed vesicovaginal fistula. Over a follow-up period ranging from 5 to 67 months, local recurrence developed in 1 patient, whereas no patient died of disease. One patient was lost to follow-up at 15 months. The 12-month disease-free survival was 88.9%, and 12-month overall survival was 100%. Stage I and selected stage II vaginal cancer patients have good outcomes in terms of survival and local tumor control if managed judiciously by initial surgery followed by selective adjuvant therapy.

Abstract A28: N-Myc drives small cell neuroendocrine cancer initiated from human prostate basal cells

Abstract Human small cell prostate carcinoma (SCPC) represents up to 25% of lethal castration-resistant prostate cancer. Molecular characterization of a panel of SCPCs recently identified frequent genomic amplification of both MYCN and AURKA. The oncogenic function of N-Myc has been characterized in many cancer types but its role in the initiation of human SCPC has not been defined. To investigate the function of N-Myc in human prostate transformation, we utilized a tissue regeneration model of human prostate cancer. Human prostate basal epithelial cells were isolated from benign primary prostate tissue from four independent human donors, infected with lentiviruses expressing the oncogenes N-Myc and activated (myristoylated) AKT1, mixed with mouse urogenital sinus mesenchyme, and grafted subcutaneously in immunodeficient NOD-SCID-IL2Rγnull mice. Palpable tumors were appreciated within 2-3 months and histological evaluation revealed regions of mixed high-grade adenocarcinoma and small cell carcinoma. The small cell carcinoma histology showed typical findings of high nuclear-to-cytoplasmic ratio, nuclear molding, stippled chromatin, and frequent mitotic and apoptotic features. Immunohistochemical analysis demonstrated low to absent androgen receptor (AR) staining in both the adenocarcinoma and small cell carcinoma. Further, we found heterogeneous staining for neuroendocrine markers including neural cell adhesion molecule 1, chromogranin A, synaptophysin, thyroid transcription factor 1, and forkhead box A2 in the regions of small cell carcinoma in support of the histological diagnosis. To assess the androgen dependence of tumor growth, regenerated N-Myc and activated AKT1 tumors derived from the lentiviral infection of primary human prostate basal cells were passaged in either intact or castrate immunodeficient mice. Tumors were propagated both in the presence and absence of androgens and showed a small but progressive enrichment of the small cell carcinoma over the adenocarcinoma with successive passage in castrate hosts. Molecular profiling by RNA-Seq of three regenerated N-Myc and activated AKT1 tumors showed a significant resemblance to a subset of human SCPC clinical specimens. Further, the adenocarcinoma and small cell carcinoma components of each tumor were remarkably similar at the transcriptional level despite their differences in histological appearance. In conclusion, we have established a novel model of human small cell prostate cancer arising from benign human prostate basal cells. Overexpression of N-Myc and activated AKT1 in basal cells produces tumors that recapitulate the histology, immunophenotype, and transcriptional profile of human SCPC. These findings support a direct role for N-Myc in the neuroendocrine transformation of basal cells in the human prostate. Further studies are ongoing to elucidate the mechanisms by which N-Myc induces a neuroendocrine differentiation program in prostate cancer. Citation Format: John K. Lee, Bryan A. Smith, John W. Phillips, Jungwook Park, Tanya I. Stoyanova, Robert Baertsch, Artem Sokolov, Colleen Mathis, Donghui Cheng, Joshua M. Stuart, Jiaoti Huang, Owen N. Witte. N-Myc drives small cell neuroendocrine cancer initiated from human prostate basal cells. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A28.