A Microsatellite in the Coding Sequence of HLA-A/B Is a Mutation Hotspot in Colon Cancer With Microsatellite Instability.
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Alleles↗
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Genomic distribution characteristics and interspecific differences of microsatellite landscapes in Felidae.
BACKGROUND: Microsatellites within genomes play crucial roles in regulating gene expression, DNA replication, and chromosomal structure and function. Analyzing the composition and distribution patterns of microsatellites in closely related species not only reveals their evolutionary dynamics and adaptive mechanisms but also provides essential technical support for applications in genetic breeding, species conservation, and disease research. As one of the world's most captivating animal groups, the landscape patterns of microsatellites across feline genomes remain to be systematically characterized. RESULTS: This study utilized high-quality genomic data to conduct a systematic comparative analysis of microsatellite landscape distribution patterns across the genomes of 13 felid species. The findings revealed that microsatellite abundance and distribution exhibit species-specific characteristics, with a non-random genomic distribution and a negative correlation between microsatellite abundance and repeat length. The predominant distribution pattern followed the sequence: single > double > quadruple > triple > quintuple > sextuple nucleotide repeats. Microsatellite abundance peaked in intergenic regions, whereas trinucleotide repeats were more prevalent within exons. Coding regions showed a marked preference for trinucleotide and hexanucleotide repeats. Enrichment analysis of GO and KEGG pathways indicated that coding sequences containing microsatellites were primarily involved in transcription and translation processes. CONCLUSIONS: Our study elucidates the distribution patterns and characteristics of microsatellites across diverse feline species, providing significant insights into their evolutionary mechanisms and functional roles. Furthermore, these findings establish a valuable reference and foundational dataset for the future development of high-quality, species-specific microsatellite markers in felids.
Animals↗
Bridging the gap between legacy polymerase chain reaction-based microsatellite data with high-throughput sequencing data for conservation genomics.
Microsatellites are powerful markers for tracking genetic variation in wildlife populations due to their high polymorphism and genome-wide abundance. While polymerase chain reaction (PCR)-based fragment size analysis has been the standard for genotyping microsatellites, high-throughput sequencing offers greater resolution and the opportunity to sync historical datasets with modern analyses. We evaluated how genotypes from whole-genome sequencing align with PCR data for 15 microsatellite loci in 11 North American brown bears (Ursus arctos). Brown bear populations in the 48 contiguous United States have declined from approximately 50,000 to fewer than 2,000 over the past decades. Their endangered status has prompted extensive research and genetic monitoring, yielding large, multiyear microsatellite datasets upon which future conservation efforts can build. We achieved an overall microsatellite genotype concordance rate of 94.5% comparing high-throughput sequencing results to PCR based-fragment size results. All discrepancies occurred at complex loci containing multiple insertions and/or deletions (indels). Physically linked indels or single nucleotide polymorphisms (SNPs) occurring within the loci were misinterpreted as independent insertions, underscoring the need for genotyping tools that incorporate phasing when genotyping. To evaluate coverage effects, we downsampled high-throughput sequence data from 30x to 2x. Concordance remained high at 20 to 30x but dropped sharply at 10x, with 5x and 2x having discordant genotypes or insufficient coverage for genotyping. Accurate genotyping required both sufficient depth and number of reads spanning the entire repeat regions. Our results show that short-read whole-genome sequencing can recover microsatellite genotypes with high accuracy when paired with careful variant interpretation. By aligning historical PCR datasets with modern sequencing data, we can preserve decades of genetic insight and strengthen long-term monitoring of at-risk populations.
Animals↗
Genetic differentiation of the supralittoral gastropod Tectarius striatus (North Atlantic Archipelagos) and development of new microsatellite resources.
Microsatellite markers are invaluable tools for assessing genetic diversity and elucidating population structure across any species. This study reports the development and application of ten novel polymorphic microsatellite loci for Tectarius striatus, a littorinid species native to the shores of Macaronesia, a geographical region that includes the archipelagos of the Azores, Madeira, Selvagens, Canary Islands, and Cabo Verde. These markers together with a portion of the COI gene were used to genotype 65 individuals, using Illumina amplicon -sequencing across five geographically distinct populations. Our analysis shows moderate to high levels of allelic diversity across all populations. Furthermore, microsatellite markers supported genetic structure between a distant population of Cabo Verde Archipelago and the northern Macaronesian archipelagos. Conversely variation of the COI showed high levels of homogeneity across the sampled populations. While the presence of null alleles and moderate levels of missing data at several loci represent challenges to this study, the overall consistency of our results with earlier research underscores the reliability of microsatellite markers for population genetic inference in this marine gastropod. Nevertheless, our findings highlight the need for cautious interpretation of diversity estimates and population structure metrics, particularly when null alleles are frequent, and underscore the value of expanding the panel of available microsatellite markers for Tectarius striatus and related taxa to improve resolution and accuracy for future studies.
Animals↗
Reference-Free Microsatellite Instability Detection from Tumor Sequencing Using Intrasample Variability Modeling.
Microsatellite instability (MSI) is a predictive biomarker in several tumor types. However, many next-generation sequencing-based callers require matched normal samples, reference panels, or pretrained models, limiting their portability across assays and sequencing centers. We developed PROMIS (PROfiling of Microsatellite InStability), a tumor-only, reference-free pipeline that uses a discrete mixture model to characterize intrasample repeat-length distributions at predefined microsatellite loci. Locus-level classifications are then aggregated into a continuous MSI score. We benchmarked PROMIS in colorectal (CRC), endometrial (UCEC), and gastric (STAD) cancers from The Cancer Genome Atlas. PROMIS achieved an overall area under the receiver operating characteristic curve (AUC) of 0.995 and cohort-specific AUCs of 1.00 in CRC and stomach adenocarcinoma and 0.999 in uterine corpus endometrial carcinoma, comparable to established tools despite not using matched normals or pretrained models. Subsampling demonstrated robust performance with substantially fewer loci. In silico dilution showed progressively reduced MSI-microsatellite-stable discrimination, with the pooled AUC declining from 0.83 at 10% tumor fraction to 0.53 at 1%. At low tumor fractions, tumor-type-specific baseline microsatellite variability increasingly influenced PROMIS scores. Finally, in prostate and CRC cell-free DNA cohorts, including Illumina TSO500 data and an 18-gene panel, PROMIS yielded MSI scores concordant with orthogonal tissue- and panel-based classifications across the evaluated Illumina-based sequencing contexts. Accordingly, the present validation should be considered limited to Illumina-based sequencing platforms. PROMIS is intended to complement existing genomic profiling workflows by enabling MSI assessment from sequencing data already generated for broader molecular analyses. Prospective clinical validation remains necessary before clinical implementation.
Journal Article↗
Resolving taxonomic complexity in the genus Boechera (Brassicaceae) using the Boechera Microsatellite Website: a case study of the rare triploid B. bodiensis.
BACKGROUND AND AIMS: The genus Boechera (rock cress) comprises ∼75 sexual diploid taxa and >355 genetically distinct hybrid lineages, many of which reproduce asexually through apomixis. This complex reproductive landscape poses substantial challenges for taxonomy, similar to those encountered in genera such as Taraxacum, Hieracium, Poa and Rubus. The Boechera Microsatellite Website (BMW) offers an extensive database and analytical tools that are proving instrumental in resolving these difficulties. Here, we demonstrate the utility of the BMW through analysis of Boechera bodiensis, a rare and poorly understood species endemic to the western Great Basin of the USA. METHODS: First described as Arabis bodiensis by Rollins in 1982, this taxon is sparsely represented in herbaria and has long been considered a candidate for protection under the Endangered Species Act. However, its taxonomic identity has remained uncertain owing to morphological similarities with other 'Arabis' (Boechera) taxa. We integrate microsatellite DNA data from the BMW with morphological analyses to provide a clearer understanding of the taxonomic status, distribution and evolutionary origins of B. bodiensis. KEY RESULTS: Pollen studies reveal that B. bodiensis is a diplosporous apomict. Microsatellite genotyping of the holotype confirms it to be triploid, containing three subgenomes derived from Boechera cobrensis, B. fernaldiana and B. sparsiflora. Expanded microsatellite surveys detect this triploid genotype at 22 additional sites, primarily in Mono County, CA, USA. Morphological analyses of genetically verified specimens identify a consistent set of characters that distinguish B. bodiensis from co-occurring congeners. CONCLUSIONS: The BMW enables high-resolution analyses of genome composition, reproductive mode and hybrid origins, making it a powerful tool for resolving taxonomic complexity in Boechera. Our case study of B. bodiensis highlights the effectiveness of combining molecular and morphological data to clarify species boundaries, inform conservation assessments and refine nomenclatural understanding in this notoriously difficult genus.
Microsatellite Repeats↗
Microsatellites Versus Genome-Wide SNPs Data for Pedigree Reconstruction in Twin Simmental Crossbred Cattle.
Accurate pedigree reconstruction is critical for genetic evaluation in admixed cattle populations, yet the relative performance of microsatellite and genome-wide SNP markers in twin-rich herds with incomplete pedigree records remains unclear. We compared 12 ISAG-recommended microsatellite markers with whole-genome SNP data for dam-calf assignment in a Simmental crossbred population (n = 43, 13 dam-calf groups) from southern China. Twin zygosity was determined from SNP identity-by-descent (PI_HAT) values: nine calf pairs were dizygotic, one pair was monozygotic (20A/21A), and one adult pair was composed of dizygotic twin sisters (31A/34A). Admixture analysis at K = 3 revealed ancestry proportions of 50.7% European taurine, 28.9% Chinese indicine and 20.4% East Asian taurine. The SNP-based neighbor-joining tree correctly recovered 12 of 13 groups (92.3%, 95% CI: 64.0-99.8%), whereas the microsatellite-based tree recovered 11 (84.6%, 95% CI: 54.6-98.1%); the difference was not statistically significant (exact McNemar test, p = 1.0). Locus INRA023 was monomorphic (PIC = 0), reducing the effective number of markers to 11. These results indicate that genome-wide SNPs show a favourable trend in accuracy and are less prone to false-positive clustering than a standard microsatellite panel in admixed, twin-rich cattle populations.
SNP↗
Genetic inference in social insects: The continued utility of microsatellites in the sociogenomic era.
Social insects differ from many other biological systems because colonies function as integrated reproductive, ecological, and evolutionary units, often conceptualized as superorganisms. This organization makes genetic inference inherently hierarchical, often requiring genotyping across multiple biological levels: the colony, the population, the individual, and, in some cases, the cellular level. Although whole-genome sequencing and single-nucleotide polymorphism (SNP)-based approaches are now widely used in population genomics, microsatellites or short tandem repeats (STRs) remain a useful approach for cost-effective, low-input, and highly replicated genotyping, particularly in the hierarchical sampling designs common in social insect studies. Here, we review the utility and limitations of microsatellites in social insect research using a three-tiered framework spanning colony-, population-, and individual- or cellular-level analyses. Across these scales, microsatellites are especially valuable for colony delimitation, kinship inference, diagnostic screening of known reproductive systems, and low-input genotyping. By comparing the suitability of microsatellites with that of SNP-based and broader genomic approaches across these applications, this review links marker choice to biological scale, sampling design, and inferential goal in studies of social insects.
Journal Article↗
Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status.
OBJECTIVES: Metastatic castration-resistant prostate cancer has a poor prognosis. Although olaparib has demonstrated efficacy in patients with BRCA1/2 mutations, real-world data in Japanese patients remain limited. We aimed to evaluate the efficacy and safety of olaparib in patients with BRCA-mutated metastatic castration-resistant prostate cancer and explore the association of BRCA2 loss and microsatellite instability status with treatment outcomes. METHODS: We conducted a multicenter retrospective study of 34 patients with BRCA-mutated metastatic castration-resistant prostate cancer treated with olaparib between December 2020 and December 2024. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, prostate-specific antigen-50 response rate, and safety. Exploratory analyses were performed. RESULTS: Among the 34 patients, 33 had a BRCA2 mutation and one had a BRCA1 mutation. Prostate-specific antigen reduction was observed in 76.4% of patients; prostate-specific antigen-50 response rate was 58.8%. Median progression-free and overall survival were 15.8 and 35.1 months, respectively. Grade ≥ 3 adverse events (most commonly anemia) occurred in 17.6% of patients. Treatment discontinuation due to adverse events occurred in one patient. Exploratory analyses were performed in 23 BRCA2-mutated patients who underwent comprehensive genomic profiling. BRCA2 loss was observed in 39.1% of patients and showed a trend toward prolonged progression-free survival, whereas microsatellite instability-high status was observed in 13.0% and was associated with shorter progression-free survival. CONCLUSIONS: Olaparib demonstrated efficacy and safety in Japanese patients with BRCA-mutated metastatic castration-resistant prostate cancer. Exploratory analyses revealed that BRCA2 loss may be associated with prolonged progression-free survival, whereas microsatellite instability-high status may be associated with shorter progression-free survival. These findings require validation in larger cohorts.
Humans↗
Development and Characterization of Microsatellite Markers for the Euryhaline Polychaete Laeonereis acuta (Annelida: Nereididae) in the Southwestern Brazilian Coast.
Laeonereis acuta is a polychaete species typically found at high abundance in estuarine and coastal lagoon environments. Due to its association with polluted habitats, it is commonly used in ecotoxicological studies. Moreover, its occurrence in spatially discontinuous environments with high environmental variability makes it a suitable model for evolutionary studies of local adaptation, genetic landscape, and early stages of speciation. This study aimed to develop primers and characterize microsatellite markers for L. acuta sampled from three coastal lagoons in southwestern Brazil. A total of 10 loci were characterized based on the genotyping of 40 individuals. The number of alleles per locus ranged from 2 to 19. Evidence of null alleles was detected at five loci, although their frequency decreased when coastal lagoons were analyzed separately. When considering all individuals as a single population, five loci showed positive and significant FIS values, and seven loci deviated from Hardy-Weinberg equilibrium. Maricá and Guarapina exhibited heterozygote excess at several loci, whereas Jaconé showed evidence of population genetic isolation. The 10 microsatellite loci were polymorphic and suitable for population genetic analysis in L. acuta, although these patterns may not necessarily be representative of other geographic regions. These markers may contribute to ecotoxicological studies by clarifying whether physiological responses to pollutants are associated with genetic differentiation among populations. Furthermore, they provide valuable tools for investigating genetic structure and connectivity in discontinuous environments.
Animals↗
A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling.
BACKGROUND/AIM: Microsatellite-stable (MSS) colorectal cancer (CRC) generally responds poorly to immune checkpoint blockade, but some MSS tumors are T-cell rich. We examined whether such infiltration reflected effective immunity or functional immune constraint. CASE REPORT: A 77-year-old woman underwent resection of a mismatch repair-proficient (pMMR), MSS, low-mutational-burden CRC with a synchronous adenoma. Whole-exome sequencing of tumor, adenoma and adjacent normal tissue detected no shared high-confidence somatic mutations between tumor and adenoma within the sensitivity of this WES analysis and identified tumor-specific APC, KRAS and TP53 alterations. Tumor single-cell RNA sequencing yielded 7,569 cells, with T-lineage populations comprising 83.5%. Cytotoxic T cells showed cytolytic and dysfunction-associated features, regulatory T cells (Tregs) showed suppressive remodeling, and Th17 cells showed inflammatory/profibrotic programs. CellChat nominated stromal MIF/FN1-CD74/CD44 and extracellular-matrix communication with T-cell compartments. CONCLUSION: This molecular case report shows that T-cell abundance and immune effectiveness can be uncoupled in MSS CRC.
Humans↗
Integrated Multiomics Analysis of Microsatellite Instability-High Colorectal Cancer Identifies a Subtype With Poor Outcome.
Up to 50% of patients with metastatic microsatellite instability-high (MSI-H) colorectal cancer (CRC) are resistant to immunotherapy and experience progression or recurrence after treatment. We integrated the genomic, epigenomic, transcriptomic, and proteomic data for 99 patients in a Chinese MSI-H CRC cohort. Proteomic profiling of primary tumors clearly classified MSI-H tumors into 2 subtypes. We found that the 2 subtypes have different mutational signatures, enriched pathways, gene fusion networks, and clinical outcomes. Notably, NCAM1 could serve as a potential biomarker for checkpoint inhibitor response in MSI-H CRC. Thus, there is an urgent need to stratify the MSI-H group into different subtypes and adopt more targeted therapies to prolong patient survival.
Humans↗
Uptake of germline testing for Lynch Syndrome in patients with deficient mismatch repair/ microsatellite-high colorectal cancer in the public hospital system in South Australia.
Lynch syndrome (LS) accounts for approximately 4% of colorectal cancer (CRC) cases and arises from pathogenic variants in mismatch repair (MMR) genes. Australian guidelines recommend universal MMR or microsatellite instability (MSI) screening in all CRC patients; however, real-world uptake remains variable. This study evaluated rates of MMR/MSI screening, germline testing, and genetics referrals across two major public hospitals in South Australia. A retrospective review of 1775 patients discussed at colorectal multidisciplinary team meetings in the Royal Adelaide and Queen Elizabeth hospitals between January 2021 and December 2023 was conducted to identify rates of MMR/MSI screening and subsequent referral of eligible patients to genetics. Of the 1129 colorectal cancer cases identified, MMR/MSI testing was performed in 93.2% (1052/1129), with deficiency detected in 12.5% (131/1052). Of these, 37% (49/131) were eligible for genetics referral after exclusion of somatic causes. Among eligible patients, 73.5% (36/49) were referred, and 43% (21/49) underwent germline testing. LS was confirmed in 12 patients (9% of deficient MMR CRC), while 9 patients (6.9%) were classified as having Lynch-like syndrome. Despite high screening rates, gaps remain in genetics referral and testing. Barriers included lack of reflex testing, loss to follow-up, and patient refusal. Targeted system-level interventions and improved genomic education are needed to enhance adherence to guidelines and optimise patient outcomes.
Humans↗
The histone modifier KAT2A presents a selective target in a subset of well-differentiated microsatellite-stable colorectal cancers.
Lysine acetyltransferase 2 A (KAT2A) plays a pivotal role in epigenetic gene regulation across various types of cancer. In colorectal cancer (CRC), increased KAT2A expression is associated with a more aggressive phenotype. Our study aims to elucidate the molecular underpinnings of KAT2A dependency in CRC and assess the consequences of KAT2A depletion. We conducted a comprehensive analysis by integrating CRISPR-Cas9 screening data with genomics, transcriptomics, and global acetylation patterns in CRC cell lines to pinpoint molecular markers indicative of KAT2A dependency. Additionally, we characterized the phenotypic effect of a CRISPR-interference-mediated KAT2A knockdown in CRC cell lines and patient-derived 3D spheroid cultures. Moreover, we assessed the effect of KAT2A depletion within a patient-derived xenograft mouse model in vivo. Our findings reveal that KAT2A dependency is closely associated with microsatellite stability, lower mutational burden, and increased molecular differentiation signatures in CRC, independent of the KAT2A expression levels. KAT2A-dependent CRC cells display higher gene expression levels and enriched H3K27ac marks at gene loci linked to enterocytic differentiation. Furthermore, loss of KAT2A leads to decreased cell growth and viability in vitro and in vivo, downregulation of proliferation- and stem cell-associated genes, and induction of differentiation markers. Altogether, our data show that a specific subset of CRCs with a more differentiated phenotype relies on KAT2A. For these CRC cases, KAT2A might represent a promising novel therapeutic target.
Humans↗
Development of Microsatellite Marker System to Determine the Genetic Diversity of Experimental Chicken, Duck, Goose, and Pigeon Populations.
Poultries including chickens, ducks, geese, and pigeons are widely used in the biological and medical research in many aspects. The genetic quality of experimental poultries directly affects the results of the research. In this study, following electrophoresis analysis and short tandem repeat (STR) scanning, we screened out the microsatellite loci for determining the genetic characteristics of Chinese experimental chickens, ducks, geese, and pigeons. The panels of loci selected in our research provide a good choice for genetic monitoring of the population genetic diversity of Chinese native experimental chickens, ducks, geese, and ducks.
Animals↗
Integrating clinical and genomic features to predict response to neoadjuvant therapy in microsatellite-stable rectal cancer.
BACKGROUND: Neoadjuvant therapy (NAT) has shifted rectal cancer management toward organ preservation. However, achieving a complete response (CR) for "watch-and-wait" strategies is hindered by high response heterogeneity. Although immunotherapy-combined NAT has expanded the candidate pools, the predictive significance of molecular alterations remains unclear. OBJECTIVES: This study aimed to evaluate clinical and genomic profiles of rectal cancer patients undergoing NAT to identify response predictors and to develop a nomogram for estimating CR probability. DESIGN: Retrospective, single-center cohort study. METHODS: This study included 437 patients with rectal adenocarcinoma at Fudan University Shanghai Cancer Center between December 2019 and March 2023. Patients underwent paired tumor and germline genomic sequencing (887-gene panel) before NAT. Logistic and Cox regression analyses were performed to identify clinical and genetic risk factors associated with tumor response and long-term survival. RESULTS: Of the 437 patients, 96.6% had microsatellite-stable (MSS) tumors. In the MSS locally advanced rectal cancer cohort (N = 307), the CR rate was 35.5%. Multivariate analysis identified immunotherapy-combined NAT (iTNT) (OR 4.41, 95% CI: 2.42-8.27), SYNE1 mutation (OR 2.12, 95% CI: 1.06-4.26), negative mesorectal fascia (MRF) status (OR 0.34, 95% CI: 0.17-0.66), and lower tumor location (OR 0.48, 95% CI: 0.27-0.84) as independent predictors of CR. KRAS mutation was the sole independent predictor of reduced disease-free survival (DFS; HR 1.93, 95% CI: (1.11-3.36), p = 0.020). KRAS G12D subtype was associated with the worst 2-year distant metastasis-free survival (71.3%) and exhibited a distinct predilection for lung metastasis. The clinical-genomic nomogram yielded strong discrimination (AUC = 0.705) and calibration, with favorable DCA net benefit. CONCLUSION: Clinical and genomic features jointly determine outcomes in MSS rectal cancer. SYNE1 mutation serves as a novel biomarker for CR, while KRAS mutations, especially the G12D subtype, identify patients at high risk for systemic relapse. The clinical-genomic nomogram facilitates individualized selection for organ-preservation strategies.
biomarker↗
Clinicopathologic Features, Treatment Patterns, and Outcomes of Microsatellite Instability-High Gastric and Gastroesophageal Junction Adenocarcinoma: A Single-Institution Retrospective Analysis.
PURPOSE: Microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) gastric or gastroesophageal junction (GEJ) adenocarcinomas are biologically distinct tumors with established sensitivity to immune checkpoint inhibitors (ICIs). However, real-world treatment patterns, response heterogeneity, and predictors of durable benefit remain poorly defined. METHODS: We retrospectively analyzed patients with biopsy-confirmed MSI-H/dMMR gastric/GEJ adenocarcinoma treated at a single center. Clinicopathologic, genomic, treatment, and outcome data were collected. Molecular profiling included ARID1A, RNF43, TP53, PIK3CA, KRAS, TGFBR2, and human epidermal growth factor 2 (HER2). ICIs-treated patients were classified as achieving clinical benefit (complete response, partial response, or durable stable disease ≥16 weeks) or no clinical benefit using iRECIST v1.1 and clinical assessment. Overall survival (OS) was estimated by using the Kaplan-Meier method. RESULTS: Thirty-four patients were identified (median age, 66 years; 53% male), including 21 with stage IV disease. Tumors were predominantly poorly differentiated (65%) and HER2-negative (94%), and 18% of patients had Lynch syndrome. Among 22 ICI-treated patients, 55% achieved clinical benefit, which was strongly associated with prolonged OS (P < .01). Most responses occurred at the first radiographic assessment (approximately 12 weeks). Elevated tumor mutational burden (TMB; ≥20 mutations/Mb) was present in 56% of patients but was not associated with clinical benefit (P = .40), and no individual genomic alteration significantly correlated with treatment outcome. Exploratory analyses suggested longer OS among patients with liver versus peritoneal metastases. Treatment was well tolerated, with predominantly low-grade immune-related adverse events. Baseline Eastern Cooperative Oncology Group performance status (0-1 v ≥ 2) was associated with clinical benefit (P = .049). CONCLUSION: Approximately half of the patients with MSI-H/dMMR gastric/GEJ adenocarcinoma cancers derived durable clinical benefit from ICIs, and treatment response was strongly associated with survival. Conventional genomic features, including TMB, did not predict clinical benefit, highlighting the need for additional biomarkers.
Humans↗
Microsatellite instability in penile cancer: comparative analysis of primary tumors and metastases.
BACKGROUND: Penile cancer (PeCA) presents high morbidity and mortality and is more prevalent in underdeveloped countries. The presence of nodal metastasis at diagnosis or as early recurrence carries a worse prognosis, making it important to determine whether clinically relevant biomarkers are maintained between primary tumors and corresponding lymph node metastases. We aim to describe the presence of DNA microsatellite instability (MSI) in primary PeCA tumors and locoregional lymph nodes affected by metastatic cells, as well as to assess HPV status through p16 expression. METHODS: A total of 116 patients were comparatively evaluated between the primary tumor and lymph node metastases. The evaluation of p16 and mismatch repair proteins was done by immunohistochemistry, and MSI status was assessed using a hexa-plex marker by polymerase chain reaction, followed by fragment analysis. RESULTS: All patients underwent a standard lymphadenectomy (inguinal or pelvic), with a pN0 frequency of 33.6%. MSI-H was found in three patients (2.6%), with correspondence between the presence of the biomarker in the primary tumors and the lymph node metastases. A second validation was performed using IHC for MMR, with MLH1/PMS2 loss in MSI-H cases. 22.8% of patients expressed p16 by immunohistochemistry. p16 positivity was associated with a 55% reduction in the risk of death. All MSI-H patients were p16 positive. CONCLUSION: MSI-H occurs in 2,6% of the sample and is associated predominantly with MLH1/PMS2 loss and p16 positivity. Together, these findings suggest potential interactions between HPV- associated carcinogenesis and genomic instability. Further prospective, biomarker-driven trials are warranted to define their prognostic and therapeutic relevance in PeCA.
HPV↗