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Cancer Medicine Oct 2023To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)-low...
Analysis of clinicopathological characteristics and prognostic factors of early-stage human epidermal growth factor receptor 2 (HER2)-low breast cancer: Compared with HER2-0 breast cancer.
PURPOSE
To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)-low expression.
METHODS
The clinicopathological data and follow-up information of EBC patients with HER2-low and HER2-0 expression treated at the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017 were analyzed. The prognosis between HER2-low and HER2-0 expression groups and with different hormone receptor (HR) expression were compared by statistics. Meanwhile, the expression of Ki67, androgen receptor (AR), TOPIIa, P53, PTEN, and CK5/6 were also analyzed with the HER2-low expression and prognosis.
RESULTS
Retrospectively analyzed 1253 cases of EBC, including 583 (46.5%) cases of HER2-low breast cancer (BC) and 366 (29.2%) HER2-0 BC cases. Among the HER2-low BC patients, 487 (83.5%) were HR-positive, while 96 (16.5%) were HR-negative. Among the HER2-0 BC patients, 265 (72.4%) were HR-positive, while 101 (27.6%) were HR-negative. Median follow-up time was 53 months. The 5-year disease-free survival of HER2-low BC patients was 90.2% (95% confidence interval [CI]: 87.2-93.1), and the 5-year overall survival was 95.4% (95% CI: 93.3-97.6). Cox regression analysis showed that T stage, lymphovascular invasion, and/or perineural invasion were prognostic factors of HER2-low BC patients. However, the 5-year disease-free survival and overall survival of patients in the HER2-low and HER2-0 groups were not significantly different in all patients, but a tendency of better prognosis in HER2-low group was seen in HR-negative tumors.
CONCLUSION
HER2-low EBC patients accounted for 46.5% of the patient population. T stage, lymphovascular invasion, and/or perineural invasion were factors affecting the prognosis of BC patients with low HER2 expression. No significant difference in prognosis was noted between HER2-low and HER2-0 EBC patients. But in HR-negative tumors, a tendency of better prognosis was seen in HER2-low versus HER2-0.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; Prognosis; Receptor, ErbB-2; Retrospective Studies
PubMed: 37772432
DOI: 10.1002/cam4.6571 -
Frontiers in Neuroanatomy 2023Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical...
Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resiniferatoxin (RTX) directly on uninjured L3 and L4 nerves alleviated thermal and mechanical hypersensitivity resulting from L5 nerve injury. Herein, using immunohistochemistry, Western blot, and qRT-PCR techniques, we reveal that perineural application of RTX (0.002%) on the L4 nerve substantially downregulated the expression of its receptor (Trpv1) and three different voltage-gated ion channels (Nav1.9, Kv4.3, and Cav2.2). These channels are found primarily in small-sized neurons and show significant colocalization with Trpv1 in the dorsal root ganglion (DRG). However, RTX treatment did not affect the expression of Kv1.1, Piezo2 (found in large-sized neurons without colocalization with Trpv1), and Kir4.1 (localized in satellite cells) in the ipsilateral DRGs. Furthermore, RTX application on L3 and L4 nerves reduced the activation of c-fos in the spinal neurons induced by heat stimulation. Subsequently, we investigated whether applying RTX to the L3 and L4 nerves 3 weeks before the L5 nerve injury could prevent the onset of neuropathic pain. Both 0.002 and 0.004% concentrations of RTX produced significant analgesic effects, while complete prevention of thermal and mechanical hypersensitivity required a concentration of 0.008%. Importantly, this preventive effect on neuropathic manifestations was not associated with nerve degeneration, as microscopic examination revealed no morphological changes. Overall, this study underscores the mechanisms and the significance of perineural RTX treatment applied to adjacent uninjured nerves in entirely preventing nerve injury-induced neuropathic pain in humans and animals.
PubMed: 38099210
DOI: 10.3389/fnana.2023.1306180 -
The British Journal of Radiology Sep 2023
Topics: Humans; Acetabulum; Hip Joint; Cysts; Magnetic Resonance Imaging; Tarlov Cysts
PubMed: 37183867
DOI: 10.1259/bjr.20221045 -
Prognostic Significance of Histopathological Parameters for Salivary Gland Adenoid Cystic Carcinoma.Dentistry Journal Nov 2023Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior,... (Review)
Review
Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.
PubMed: 37999026
DOI: 10.3390/dj11110262 -
The Journal of Urology Jul 2023Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to...
PURPOSE
Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to identify subgroups of men who can safely remain on active surveillance despite preoperative reclassification to Grade Group 2.
MATERIALS AND METHODS
We studied 249 active surveillance patients with surveillance biopsies classified as Grade Group 1 or Grade Group 2 who underwent radical prostatectomy. Perineural invasion, cancer volume, linear length and maximum percentage of Gleason pattern 4, and prostate-specific antigen density were evaluated. Radical prostatectomy adverse pathology was defined by any of: pN1; ≥pT3; ≥Grade Group 2 with ≥20% Gleason pattern 4; intraductal carcinoma; large cribriform glands.
RESULTS
A multivariable logistic regression model incorporating prostate-specific antigen density and perineural invasion stratified radical prostatectomy adverse pathology risk among Grade Group 1 and Grade Group 2 active surveillance patients. 57% (39/68) of Grade Group 1 men reclassified to Grade Group 2 while on active surveillance had favorable radical prostatectomy pathology. Those without biopsy perineural invasion and with low prostate-specific antigen density were more likely to have favorable radical prostatectomy pathology.
CONCLUSIONS
Most Grade Group 1 men who enter active surveillance and subsequently reclassify to Grade Group 2 have favorable findings at radical prostatectomy and can remain on active surveillance. Among patients reclassified to Grade Group 2, those with low prostate-specific antigen density and without perineural invasion had the lowest risk of radical prostatectomy adverse pathology, comparable to (or below) that of Grade Group 1 patients who were not reclassified to Grade Group 2 preoperatively. Prostate-specific antigen density and perineural invasion stratify risk in active surveillance patients reclassified to Grade Group 2 and, if concordant with other clinicopathological and radiographic findings, can enable more patients to remain on active surveillance. Reclassification to Grade Group 2 alone should not disqualify men from remaining on active surveillance.
Topics: Male; Humans; Prostate-Specific Antigen; Watchful Waiting; Prostatic Neoplasms; Prostate; Prostatectomy; Biopsy; Neoplasm Grading
PubMed: 37042826
DOI: 10.1097/JU.0000000000003461 -
Journal of Biochemical and Molecular... Apr 2024The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is... (Review)
Review
The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer-associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene-related peptide which is also involved in pain. Matrix metalloproteases are the zinc-associated proteases enzymes which activates proinflammatory interleukin-1β into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below.
Topics: Humans; Substance P; Neuralgia; Pancreas; Pancreatic Neoplasms; Fibroblasts; Tumor Microenvironment
PubMed: 38613466
DOI: 10.1002/jbt.23638 -
The Journal of Urology Jul 2023While active surveillance is the preferred management for most men with low-risk prostate cancer, a subset may harbor more aggressive disease. In this review we examine... (Review)
Review
PURPOSE
While active surveillance is the preferred management for most men with low-risk prostate cancer, a subset may harbor more aggressive disease. In this review we examine the evidence underlying an accurate and nuanced assessment of oncologic risk in these men.
MATERIALS AND METHODS
We performed a nonsystematic literature review current to January 2023 on PubMed for articles relating to clinical, pathological, molecular, and imaging-based modalities available for risk assessment in men with low-risk prostate cancer. Relevant articles were reviewed by the authors and evidence was summarized.
RESULTS
Many tools are available to personalize clinical decision-making for men with low-risk prostate cancer. Total volume of cancer, PSA density, and presence of ductal components have been consistently and strongly associated with current or future evidence of higher-grade disease. PSA kinetics, Prostate Imaging Reporting & Data System 4/5 lesions on MRI, perineural invasion, germline mutations, and genomic classifiers all appear to be associated with an increased risk, although are not as extensively validated. Race, percent free PSA, and other serum biomarkers such as Prostate Health Index and 4Kscore do not appear to be associated with long-term elevated risk.
CONCLUSIONS
Long-term prognosis for men diagnosed with low-risk prostate cancer is excellent. There are many factors which should be routinely integrated into the initial management decision as well as determining intensity and frequency of active surveillance. Development of comprehensive multivariable instruments to guide clinical decisions is encouraged.
Topics: Male; Humans; Prostate-Specific Antigen; Watchful Waiting; Prostatic Neoplasms; Prostate; Risk Assessment
PubMed: 37042807
DOI: 10.1097/JU.0000000000003454 -
Virchows Archiv : An International... Aug 2023Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of...
Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of disease. PNI is currently considered as a "present vs. absent" feature, and a severity score system has not yet been established. The aim of the present study was thus to develop and validate a score system for PNI and to correlate it with other prognostic features. In this monocentric retrospective study, 356 consecutive PDAC patients (61.8% upfront surgery patients, 38.2% received neoadjuvant therapy) were analyzed. PNI was scored as follows: 0: absent; 1: the presence of neoplasia along nerves < 3 mm in caliber; and 2: neoplastic infiltration of nerve fibers ≥ 3 mm and/or massive perineural infiltration and/or the presence of necrosis of the infiltrated nerve bundle. For every PNI grade, the correlation with other pathological features, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed. Uni- and multivariate analysis for DFS and DSS were also performed. PNI was found in 72.5% of the patients. Relevant trends between PNI score and tumor differentiation grade, lymph node metastases, vascular invasion, and surgical margins status were found. The latter was the only parameter statistically correlated with the proposed score. The agreement between pathologists was substantial (Cohen's K 0.61). PNI severity score significantly correlated also with decreased DFS and DSS at univariate analysis (p < 0.001). At multivariate analysis, only the presence of lymph node metastases was an independent predictor of DFS (HR 2.235 p < 0.001). Lymph node metastases (HR 2.902, p < 0.001) and tumor differentiation grade (HR 1.677, p = 0.002) were independent predictors of DSS. Our newly developed PNI score correlates with other features of PDAC aggressiveness and proved to have a prognostic role though less robust than lymph nodes metastases and tumor differentiation grade. A prospective validation is needed.
Topics: Humans; Retrospective Studies; Lymphatic Metastasis; Neoplasm Invasiveness; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 37291275
DOI: 10.1007/s00428-023-03574-x -
Current Oncology (Toronto, Ont.) Sep 2023Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to... (Review)
Review
Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.
Topics: Humans; Peripheral Nerves; Neoplasm Invasiveness
PubMed: 37887547
DOI: 10.3390/curroncol30100647 -
Journal of Oral Pathology & Medicine :... Jul 2023Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas, there still have controversies and limitations regarding the...
BACKGROUND
Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas, there still have controversies and limitations regarding the standardization for its detection. In this study, we explore the impact of neural invasion in oral squamous cell carcinomas prognosis, comparing intraneural invasion (tumor cells inside nerve structure) and perineural invasion (cells involving the nerve, but not invading its sheath).
METHODS
Surgical slides stained with hematoxylin and eosin from 235 patients with oral squamous cell carcinomas were carefully verified for the presence of intraneural invasion and perineural invasion. The location in the tumor (intratumoral vs. peritumoral) and number of foci (unifocal or multifocal) were also explored. Survival analyses for cancer-specific survival and disease-free survival were performed with Cox proportional model.
RESULTS
Neural invasion was identified in 74 cases, 64.9% displayed intraneural invasion and 35.1% displayed perineural invasion. Univariate analysis revealed a significantly poorer cancer-specific survival, but not disease-free survival, in patients with intraneural invasion, in contrast to cases with perineural invasion that did not achieve significant association with both cancer-specific survival and disease-free survival. Further analyses revealed that the location in the tumor and number of foci had little impact on discriminatory ability of intraneural invasion. Multivariate analysis confirmed that intraneural invasion is significantly and independently associated with poor cancer-specific survival (hazard ratio: 2.50, 95% CI: 1.31-3.79, p = 0.003).
CONCLUSION
This study provides evidence that intraneural invasion, but not perineural invasion, is a relevant predictor of survival in patients with oral squamous cell carcinomas, suggesting that its association with other clinical and pathological prognostic factors should be consider in determining the optimal treatment protocol and prognosis of these patients.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms; Prognosis; Neoplasm Invasiveness; Head and Neck Neoplasms; Retrospective Studies
PubMed: 36850021
DOI: 10.1111/jop.13423