scholarly journals The opposing action of stromal cell proenkephalin and stem cell transcription factors in prostate cancer differentiation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alvin Y. Liu
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Small Cell Carcinoma ◽  
Disease Patient ◽  
Small Cell ◽  
Specific Factor ◽  
Down Regulation

Abstract Background Loss of prostate cancer differentiation or de-differentiation leads to an untreatable disease. Patient survival would benefit if this can be prevented or reversed. Cancer de-differentiation transforms luminal-like (differentiated) adenocarcinoma into less luminal-like and more stem-like (undifferentiated) small cell carcinoma through a sequential activation of stem cell transcription factors (scTF) POU5F1, LIN28A, SOX2 and NANOG. Like stem cells, prostate small cell carcinoma express this quartet of scTF as well as a 10-fold lower level of β2-microglobulin (B2M) than that of differentiated cell types. In organ development, prostate stromal mesenchyme cells mediate epithelial differentiation in part by secreted factors. Methods The identified prostate stromal-specific factor proenkephalin (PENK) was cloned, and transfected into scTF+B2Mlo stem-like small cell carcinoma LuCaP 145.1, reprogrammed luminal-like scTF−B2Mhi LNCaP, and luminal-like scTF−B2Mhi adenocarcinoma LuCaP 70CR. The expression of scTF, B2M and anterior gradient 2 (AGR2) was analyzed in the transfected cells. Results PENK caused down-regulation of scTF and up-regulation of B2M to indicate differentiation. When transfected into reprogrammed LNCaP, PENK reversed the reprogramming by down-regulation of scTF with attendant changes in cell appearance and colony morphology. When transfected into LuCaP 70CR, PENK up-regulated the expression of adenocarcinoma antigen AGR2, a marker associated with cancer cell differentiation. Conclusions Prostate cancer cells appear to retain their responsiveness to stromal PENK signaling. PENK can induce differentiation to counter de-differentiation caused by scTF activation. The many mutations and aneuploidy characteristic of cancer cells appear not to hinder these two processes. Loss of prostate cancer differentiation is like reprogramming from luminal-like to stem-like.

scholarly journals Small Cell Carcinoma of the Prostate in an Elderly Patient: A Case Report and Review of the Literature

Rare Tumors ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 176-178 ◽  
Author(s):  
Dale Alan Whitaker ◽  
Daniel H. Miller ◽  
Niveditha Jagadesh ◽  
Gerald W. Strong ◽  
Lauren Hintenlang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Current Knowledge ◽  
Case Reports ◽  
The United States ◽  
Small Cell ◽  
Rapid Progression ◽  
Retrospective Case

Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC), which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89-year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care.

scholarly journals Not such a small diagnosis: small cell carcinoma of the prostate

2020 ◽  
Vol 2020 (6) ◽  
Author(s):  
Abdul Rauf ◽  
Stephanie F Smith ◽  
Rono Mukherjee ◽  
Nyla Nasir
Keyword(s):  
Prostate Cancer ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Targeted Therapies ◽  
Specific Antigen ◽  
Serum Levels ◽  
Prostate Adenocarcinoma ◽  
Small Cell ◽  
Neck Swelling ◽  
Genomic Typing

Abstract Small cell carcinoma (SCC) is an aggressive malignancy most commonly described in the lung. We present a case of a 61-year-old male who presented with a neck swelling and was subsequently found to have metastatic SCC of the prostate. Clinicians should be aware that it metastasizes early. Unlike conventional prostate adenocarcinoma, it is not a prostate-specific antigen (PSA) secreting tumor hence serum levels do not correlate with disease severity, and a low PSA reading may give false reassurance. In the future, further studies on genomic typing and novel targeted therapies may achieve better clinical outcomes for patients with this aggressive type of prostate cancer.

Primary genitourinary small cell carcinoma: Clinicopathologic and survival outcomes from SEER database.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 200-200
Author(s):  
R. Thota ◽  
S. Birdsong ◽  
S. Subbiah
Keyword(s):  
Prostate Cancer ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Renal Cancer ◽  
Small Cell ◽  
External Beam Radiation ◽  
Seer Database ◽  
Specific Mortality ◽  
Cancer Specific Mortality

200 Background: Small cell carcinoma of genitourinary system (SCC) is a highly aggressive and rare entity. The aim of the study is to characterize the clinicopathologic characteristics and evaluate the treatment outcomes of SCC in adult patients. Methods: Retrospective analysis of 732 patents diagnosed with small cell carcinoma of bladder from 1973 to 2007 was done via SEER database. Demographics, stage, type of treatment received and cancer-specific mortality were examined. Results: 732 patients were identified with SCC of genitourinary tract of which 341 were small cell bladder cancer, 336 were small cell prostate cancer and 55 were small cell renal cancer. Of these 644 patients were males and 88 were females. Median age of diagnosis is 73 years for bladder, 72 years for prostate and 70 years for renal cancer. Majority of the patients were Caucasians (89%) followed by African Americans (6%) and other races (4.98%). Grading of the tumor revealed that 12 patients had well differentiated tumor, 18 patients had moderately differentiated tumor, 191 patients had poorly differentiated, 292 patients had undifferentiated tumor and 219 patients had unknown grade. Pathological T-stages were as follows: T1= 34 (4.6%), T2= 102 (14%), T3= 43 (9%), T4= 41 (5.6%), 38.4% unknown T stage and 67 (9%) patients had metastatic disease. In majority of the patients the treatment received was unknown (565), 90 patients received external beam radiation, and 76 patients received surgery. Cancer-specific mortality was 54% in bladder cancer, 71% in prostate cancer and 78.6% in renal cancer. Median overall survival for all stages was 15.8 months in bladder cancer, 11.3 months in prostate cancer and 8 months in renal cancer. Conclusions: Results show that SCC is a highly aggressive tumor with poor prognosis. Clinical trials involving multiple institutes are needed to accrue enough patients so that treatment paradigms for this uncommon disease can be developed. No significant financial relationships to disclose.

scholarly journals Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
XiaoJun Lu ◽  
Wenwen Gao ◽  
Yu Zhang ◽  
Tao Wang ◽  
Hongliang Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Carcinoma ◽  
Seminal Vesicle ◽  
Small Cell Carcinoma ◽  
Cell Cancer ◽  
Phylogenetic Reconstruction ◽  
Neuroendocrine Differentiation ◽  
Small Cell ◽  
Castration Resistance ◽  
Tumor Biopsy

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

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