Genomic Alterations In T
Small Cell Carcinoma of the Prostate Explained
Unlike other small cell neuroendocrine carcinomas and their non-small cell histologic counterparts, there is a surprising overlap in the spectrum of genomic alterations seen in t-SCNC and mCRPC-adenocarcinoma. Similar numbers of single nucleotide and copy number variants are observed across t-SCNC and mCRPC-adenocarcinoma specimens, and most of the common PC alterations are detected in similar frequencies across the two histologic subtypes. This genomic overlap supports a divergent model of clonal evolution, whereby t-SCNC arises through transdifferentiation of an mCRPC-adenocarcinoma subclone – rather than treatment selection of a pre-existing independent neuroendocrine subclone. The paucity of genomic differences between mCRPC-adenocarcinoma and t-SCNC also underscores the potential role of epigenetic reprogramming in mediating lineage plasticity and establishing tumor phenotype, discussed below. In the context of this broad genomic overlap, however, the few genomic differences that have been described across the two histologic subtypes provide important insights into the pathogenesis of t-SCNC. Gene Expression Profiling Of Scpc/lcnec Xenografts Reveals Upregulation Of Mitotic GenesUnsupervised hierarchal clustering of the raw expression profiles obtained from the MDA PCa 79, 117-9, 130, 144-13, 144-4, 146-10, 155-2, and 155-12 xenografts showed that replicates from the same xenograft clustered together, reflecting biologic identity, and that the xenografts were classified according to their morphology and AR expression . SCPC/LCNEC xenografts were collectively compared against the adenocarcinoma xenografts. We identified 140 probes expressed differently , corresponding to 104 unique RefSeq Transcript IDs . Gene Ontology analysis showed enrichment in mitosis-related biologic process subtrees, including âcell-cycle phaseâ , âmitotic cell cycleâ , and âcell divisionâ , among the 104 genes expressed differently between the groups . Genes in these subtrees included CDC25C , ANLN , AURKA , HELLS , UBE2C , PTTG1 , KPNA2 , TACC3 , PDCD6IP , HIST1H4C , and PCNA . Does Atezolizumab Boost Survival With Chemotherapy In Small Cell Or Neuroendocrine Carcinoma Of The ProstateA correlation between small cell or neuroendocrine carcinoma of the prostate and poor survival outcomes was revealed, despite treatment with the combination of the immunotherapy agent atezolizumab and chemotherapy, according to an institutional study conducted within the Mayo Clinic. A correlation between small cell or neuroendocrine carcinoma of the prostate and poor survival outcomes was revealed, despite treatment with the combination of the immunotherapy agent atezolizumab and chemotherapy, according to an institutional study conducted within the Mayo Clinics Division of Medical Oncology. The exploration of this combination in prostate cancer was influenced by the survival benefit observed with atezolizumab and chemotherapy in patients with extensive-stage small cell lung cancer . It is a common clinical practice to use regimens from the SCLC space to treat rare extrapulmonary small cell carcinoma, therefore oncologists at the Mayo Clinic sought to test the treatment strategy in their institution. Recent introduction of checkpoint inhibitor therapy for SCC of the prostate was based on extrapolation from studies in small-cell lung cancer. We wanted to review the outcomes for such patients who had received chemo-immunotherapy treatment at Mayo Clinic, the study lead Lance C. Pagliaro, MD, professor of oncology, Division of Medical Oncology, Department of Oncology at Mayo Clinic, told Targeted Oncology in an interview. Reference: Dont Miss: Healthy Foods For Your Prostate Read Also: Does Prostate Cancer Affect Libido Relationship Between Target And TherapyFor those patients with pure small cell carcinoma, SCLC regimens such as carboplatin-etoposide with or without the anti-PDL1 immune checkpoint inhibitor atezolizumab ) may also be considered. Docetaxel with carboplatin is also a reasonable option for patients who have not previously received docetaxel, given the frequent mixed CRPC/NEPC features. A major clinical challenge is in what to do next after platinum-based chemotherapy. There are limited data in the second line and beyond settings. For mixed tumors with both adenocarcinoma and NEPC elements, the choice of therapy depends on the dominant histology and clinical context. Next line SCLC regimens may be considered for those with small cell NEPC these include lurbinectedin, topotecan, pembrolizumab, ipilimumab/nivolumab. Given limited data, we would encourage participation in clinical trials. Further, ADT should be considered in both de novo and treatment-related NEPC cases given tumor heterogeneity. Citation: Endocrine-Related Cancer 28, 8 10.1530/ERC-21-0140 Coping With Small Cell Prostate CancerCoping with a rare condition can be difficult, both practically and emotionally. Being well informed about the cancer and its treatment can help you to make decisions and cope with what happens. It can also help to talk to other people who have the same condition. You can visit Cancer Chat Cancer Research UK’s discussion forum. It is a place for anyone affected by cancer to share experiences, stories and information with other people who know what you are going through.
Recommended Reading: What Is Stage 4 Prostate Cancer Where Can I Get SupportBeing diagnosed with any kind of prostate cancer can be frightening and overwhelming. If you are told you have a rare prostate cancer you may worry about what this means and feel frustrated that there isnt much information available about your diagnosis and treatment. No matter what youre feeling or thinking, there is support available if you want it. You can speak to our Specialist Nurses, in confidence or chat with them online. Our Dealing with prostate cancer page looks at things you can do to help yourself and people who can help. Visit our wellbeing hub for information to help support you in looking after your emotional, mental, and physical wellbeing. If you are close to someone with prostate cancer, find out more about how you can support someone with prostate cancer and where to get more information. What Is A 5A relative survival rate compares people with the same type and stage of cancer to people in the overall population. For example, if the 5-year relative survival rate for a specific stage of lung cancer is 60%, it means that people who have that cancer are, on average, about 60% as likely as people who dont have that cancer to live for at least 5 years after being diagnosed. You May Like: Questions To Ask Doctor When Diagnosed With Prostate Cancer Read Also: How Long Prostate Cancer Spread Diagnosing Rare Prostate CancersRarer prostate cancers can be harder to diagnose. For example, some dont cause your prostate specific antigen level to rise. This means theyre not always picked up by a PSA test. Because of this, some rare cancers may not be diagnosed until they have already spread outside the prostate. Read more about the PSA test and other tests used to diagnose prostate cancer. Some rare prostate cancers may only be picked up after having a biopsy to check for prostate cancer, or surgery called transurethral resection of the prostate to treat an enlarged prostate. The tissue removed during the biopsy or TURP is looked under a microscope to see if you have common prostate cancer or a rare type of prostate cancer. Rare cancers arent always given a Gleason score after a biopsy. This is because they can behave differently to common prostate cancer and cant be measured in the same way. Because rare cancer can be aggressive and spread outside the prostate, you will probably have more tests to see if they have spread. These include: Large Cell Prostate Cancer
Prostate Carcinoma Pathology ( Morphology and Gleason Grading)
Large cell prostate cancer is very rare. Because of this, we dont yet know how it develops, or the best ways to treat it. It is aggressive and can spread quickly to other parts of the body. Most men who have large cell prostate cancer also have common prostate cancer at the same time. And its most common in men whove already had hormone therapy for normal prostate cancer. Because neuroendocrine cells dont produce PSA, most men with large cell prostate cancer have a low PSA level. So a PSA test cant be used to diagnose or monitor your cancer. But if you have both large cell prostate cancer and common prostate cancer at the same time, you may have higher PSA levels. More research is needed before we can know whether PSA tests can help to diagnose large cell prostate cancer mixed with common cancer. Most large cell prostate cancers are diagnosed when they have grown large enough press against the urethra , which can cause difficulty urinating . So large cell prostate cancer is often diagnosed when men have surgery called transurethral resection of the prostate to treat their urinary problems. Tissue removed during surgery is looked at under the microscope to confirm you have large cell prostate cancer. You will also need scans to see if your cancer has spread. Most men with large cell prostate cancer have chemotherapy . You may also be offered surgery and radiotherapy, depending on how much the cancer has grown and spread. Also Check: Why No Caffeine Before Prostate Mri Modeling A Lethal Prostate Cancer Variant With SmallCorresponding Authors: Note: Supplementary data for this article are available at Clinical Cancer Research Online . S.N. Maity and A. Aparicio contributed equally to this work and are co-senior authors. The genomic and transcript profiling data have been deposited into NCBI/GEO under superseries GSE33054. Corresponding Authors:
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