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Pancreatology : Official Journal of the... Jun 2024Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal...
BACKGROUND/OBJECTIVES
Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients.
METHODS
Five histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed.
RESULTS
Forty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months vs. not reached (NR) (p = 0.258), while the OS was 19 months vs. NR (p = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS vs. <6 PNI + patients (29 vs. 11 months, p < 0.001) and <6 PNI+ and PNI- patients (43 vs. 11 months, p < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS vs. <6 PNI+ and PNI- patients (13 vs. 6 months, p = 0.022).
CONCLUSIONS
We report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.
Topics: Humans; Pancreatic Neoplasms; Male; Female; Aged; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Carcinoma, Pancreatic Ductal; Prognosis; Disease-Free Survival; Treatment Outcome; Aged, 80 and over; Peripheral Nerves; Adult; Survival Analysis
PubMed: 38514359
DOI: 10.1016/j.pan.2024.03.004 -
Pathology Aug 2023Penile squamous cell carcinoma (pSCC) is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor...
Penile squamous cell carcinoma (pSCC) is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor prognosis but represents a late sign, and more prognostic markers for effective patient risk stratification are urgently needed. In this retrospective study, 152 tumour samples with formalin-fixed, paraffin-embedded tissue were analysed for traditional pathological variables, tumour budding, p53, p16, and mismatch repair proteins (MMR) immunohistochemistry. The density of tumour lymphocytic infiltrate was also determined, using subjective evaluation by two pathologists (brisk/non-brisk/absent) and also using the immunoscore method, which categorised the cohort into five immunoscore groups according to the number of CD3+ and CD8+ T-cells in both the tumour centre and tumour invasion front. Only one case (0.6%) was MMR-deficient. Tumour budding count ≥5 tumour buds/20× power field and non-brisk/absent lymphocytic infiltrate were significant negative predictors of both the overall survival (OS) and cancer-specific survival (CSS), whereas a low immunoscore was a significant marker of shorter OS but not CSS. Advanced pT stage (3+4) was a significant marker of shorter CSS but not OS. In the multivariate analysis, high-grade budding was a significant parameter if adjusted for the patient's age and associated variables, except for the pN stage. The lymphocytic infiltrate retained its prognostic significance if adjusted for age and associated variables. The negative prognostic significance of the previously described parameters (lymphatic, venous, and perineural invasion, regional lymph node metastasis, and p53 mutated profile) were confirmed in our study. Grade, histological subtype, and HPV status (as determined by p16 immunohistochemistry) showed, surprisingly, little or no prognostic significance.
Topics: Male; Humans; Retrospective Studies; Tumor Suppressor Protein p53; Carcinoma, Squamous Cell; Prognosis; Penile Neoplasms; Inflammation
PubMed: 37316384
DOI: 10.1016/j.pathol.2023.03.010 -
European Journal of Dentistry Oct 2023The aim of this study was to determine the value of immune expression of p63 and cyclin D1 in the prediction of lymphovascular invasion (LVI) and perineural invasion...
OBJECTIVES
The aim of this study was to determine the value of immune expression of p63 and cyclin D1 in the prediction of lymphovascular invasion (LVI) and perineural invasion (PNI) in oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS
Clinical and histopathologic features of 65 subjects with histologically confirmed OSCC were collected. Tissue microarray blocks representing all subjects were prepared for the immunohistochemical quantification of the nuclear expression of p63 and cyclin D1 using immune ratio plugin of image J software. Image analysis was performed by two independent pathologists. Independent samples -test, analysis of variance, and receiver operating characteristic curve tests were used for statistical analysis. The level of significance was set at ≤ 0.05.
RESULTS
The optimum cutoff value for the prediction of LVI for p63 and cyclin D1 was found to be 100 and 93.2, respectively, while the optimum cutoff value for the prediction of PNI for p63 and cyclin D1 was found to be 95.9 and 94, respectively. p63 and cyclin D1 expression correlated with several clinicopathologic features of the studied population. p63 expression was a significant predictor of moderate/poorly differentiated OSCC compared with well-differentiated OSCC. A parallel combination of positive p63 and cyclin D1 increased the specificity of predicting LVI from 89.1% and 67.4% for either p63 or cyclin D1, respectively, to 93.5% with a positive predictive value of 92.5%. Similarly, the parallel combination of the two markers raised the specificity of predicting PNI from 70% and 77.5% for either p63 or cyclin D1, respectively, to 90% with a positive predictive value of 86.3%.
CONCLUSION
Combined overexpression of nuclear markers p63 and cyclin D1 can be considered as a valuable independent predictor of LVI and PNI, and hence tumor progression, in OSCC.
PubMed: 36716784
DOI: 10.1055/s-0042-1760301 -
Clinical & Experimental Metastasis Oct 2023Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4,...
Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC.
Topics: Humans; Nectins; Carcinoma, Transitional Cell; Lymphatic Metastasis; Urinary Bladder Neoplasms; Salivary Gland Neoplasms; Biomarkers; Cell Adhesion Molecules
PubMed: 37480387
DOI: 10.1007/s10585-023-10222-w -
IScience Sep 2023The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies...
The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies validating these modifications have yielded inconsistent results. The existing TNM staging system in prognostic prediction remains unsatisfactory. The prognosis of PDAC is closely associated with pathological and biological factors. Herein, we propose a new staging system incorporating distant metastasis, postoperative serum levels of CA19-9 and CEA, tumor size, lymph node metastasis, lymphovascular involvement, and perineural invasion to enhance the accuracy of prognosis assessment. The proposed staging system exhibited a strong correlation with both overall survival and recurrence-free survival, effectively stratifying survival into five distinct tiers. Additionally, it had favorable discrimination and calibration. Thus, the proposed staging system demonstrates superior prognostic performance compared to the TNM staging system, and can serve as a valuable complementary tool to address the limitations of TNM staging in prognostication.
PubMed: 37664604
DOI: 10.1016/j.isci.2023.107589 -
Biomedicines Oct 2023Tumor budding (TB) is a dynamic process associated with the epithelial-mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part...
BACKGROUND
Tumor budding (TB) is a dynamic process associated with the epithelial-mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part of the tumor microenvironment, tumor buds demonstrate increased cell motility and invasiveness. Current evidence demonstrates that high levels of TB correlate with disease progression and worst outcomes across different solid tumors. Our work aims to demonstrate the clinical applicability of TB analysis and its utility as a prognostic factor for patients with early breast cancer (EBC).
METHODS
Retrospective, single-center, observational study, enrolling patients with EBC diagnosed in a Portuguese hospital between 2014 and 2015. TB classification was performed according to the International Tumor Budding Conference 2016 guidelines.
RESULTS
A statistically significant relation was found between higher TB score and aggressive clinicopathological features (angiolymphatic/perineural invasion- < 0.001; tumor size- = 0.012; nuclear grading- < 0.001; and Ki-67 index- = 0.011), higher number of relapses ( < 0.001), and short disease-free survival (DFS) ( < 0.001).
CONCLUSION
We demonstrate that high TB correlates with shorter DFS and aggressive clinicopathological features used in daily practice to decide on the benefit of chemotherapy for EBC. TB represents a needed prognostic biomarker for EBC, comprising a new factor to be considered in the adjuvant decision-making process by identifying patients at a high risk of relapse and with higher benefit on treatment intensification. Clinical trials incorporating TB are needed to validate its prognostic impact.
PubMed: 38001907
DOI: 10.3390/biomedicines11112906 -
Frontiers in Oncology 2023Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process...
INTRODUCTION
Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.
METHODS
A431 cells were injected into the whisker pads of BALB/c and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.
RESULTS
The rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model's utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.
DISCUSSION
This model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.
PubMed: 37746297
DOI: 10.3389/fonc.2023.1231104 -
Medicine Dec 2023Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer, and have been shown with diagnostic values in various cancers. The latest... (Observational Study)
Observational Study
Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer, and have been shown with diagnostic values in various cancers. The latest research showed that hsa_circ_0124554 is closely related to liver metastasis and vascular invasion in colorectal cancer (CRC). This study aimed to investigate whether hsa_circ_0124554 can be used as a diagnostic marker for CRC. In this study, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect hsa_circ_0124554 expression levels in 40 pairs of CRC tissues and adjacent non-tumor intestinal tissues derived from CRC patients and 32 paired plasma specimens. The relationship between the expression of hsa_circ_0124554 and the clinicopathological features of CRC patients was analyzed by t-test and chi-square test. Receiver operating characteristic (ROC) curve analysis was established to explore the diagnostic value of hsa_circ_0124554 in CRC. The results showed that hsa_circ_0124554 was substantially expressed in CRC tissues (P < .001) and that there were variations in pathological differentiation, perineural invasion and invasion. The expression of hsa_circ_0124554 in CRC patients was considerably higher than healthy controls (P < .001). The area under the receiver operating characteristic (ROC) curve (AUC) of tissue and plasma hsa_circ_0124554 was 0.703 and 0.742. The AUC of the expression combined hsa_circ_0124554, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) had the best diagnostic performance (AUC = 0.899) in the CRC groups, and the sensitivity and specificity were 0.844 and 0.844. The expression of hsa_circ_0124554 was up-regulated in the tissues and plasma in CRC patients, which may be a new biomarker for the diagnosis of CRC. The combination hsa_circ_0124554, CEA and CA199 has the best diagnostic efficacy in CRC.
Topics: Humans; Carcinoembryonic Antigen; Biomarkers, Tumor; RNA, Circular; Sensitivity and Specificity; Colorectal Neoplasms
PubMed: 38050241
DOI: 10.1097/MD.0000000000036353 -
Cancer Cell International Jul 2023ST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and...
BACKGROUND
ST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and specific roles in metastatic prostate cancer (PCa) remain largely unclear.
METHODS
Two independent public datasets (TCGA-PRAD and GSE21032), containing 648 PCa samples in total, were employed to comprehensively examine the mRNA expression changes of ST6GALNAC family members in PCa, as well as their associations with clinicopathological parameters and prognosis. The dysregulation of ST6GALNAC5 was further validated in a mouse PCa model and human PCa samples from our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and drug sensitivity analyses were performed to enrich the biological processes most related to ST6GALNAC5. Sulforhodamine B, transwell, luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to examine the PCa cell proliferation, invasion and transcriptional regulation, respectively.
RESULTS
Systematical investigation of six ST6GALNAC family members in public datasets revealed that ST6GALNAC5 was the only gene consistently and significantly upregulated in metastatic PCa, and ST6GALNAC5 overexpression was also positively associated with Gleason score and predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein expression was increased in prostatic intraepithelial neoplasia and further elevated in PCa from a PbCre;Pten mouse model; (2) overexpressed ST6GALNAC5 protein was confirmed in human PCa samples comparing with benign prostatic hyperplasia samples from our cohort (p < 0.001); (3) ST6GALNAC5 overexpression was significantly correlated with perineural invasion of PCa. Moreover, we first found transcription factor GATA2 positively and directly regulated ST6GALNAC5 expression at transcriptional level. ST6GALNAC5 overexpression could partially reverse GATA2-depletion-induced inhibition of PCa cell invasion. The GATA2-ST6GALNAC5 signature exhibited better prediction on the poor prognosis in PCa patients than GATA2 or ST6GALNAC5 alone.
CONCLUSIONS
Our results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion.
PubMed: 37468844
DOI: 10.1186/s12935-023-02983-x -
Cureus Oct 2023Laryngeal cancer is predominantly a squamous cell in origin that can present with voice changes and difficulty or pain with swallowing. It is more likely to cause local...
Laryngeal cancer is predominantly a squamous cell in origin that can present with voice changes and difficulty or pain with swallowing. It is more likely to cause local spread than distant ones. The prognosis depends on multiple factors, including the stage, tumor differentiation, extranodal extension, and adjuvant therapy. Head and neck cancers have a higher tendency for perineural invasion and spread, one of the most vital factors correlating with poor outcomes and recurrence rates. We present a rare case of a 52-year-old male with an extensive history of tobacco use (five packs per day over 30 years) who developed laryngeal squamous cell carcinoma that spread to the brain despite total laryngectomy and adjuvant radiation therapy. Despite resection of the brain metastasis, the tumor metastasized again in the brain through perineural spread. Due to the side effects of repeated radiotherapy and starting chemotherapy, the patient opted for comfort care and refused further treatment. The perineural spread of head and neck cancers is not abundant in the literature, and we believe our case will add to the future treatment of head and neck cancers with perineural invasion.
PubMed: 37942386
DOI: 10.7759/cureus.46676