Prognosis and Progression of ESCC Patients with Perineural Invasion.
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ABSTRACT:
SUBMITTER: Xu G
PROVIDER: S-EPMC5335559 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Prognosis and Progression of ESCC Patients with Perineural Invasion.
Xu Guanghui G Feng Fan F Liu Zhen Z Liu Shushang S Zheng Gaozan G Xiao Shuao S Cai Lei L Yang Xuewen X Li Guocai G Lian Xiao X Guo Man M Sun Li L Yang Jianjun J Fan Daiming D Lu Qun Q Zhang Hongwei H
Scientific reports 20170303
Perineural invasion (PNI) has been recognized as a poor prognostic factor in several malignancies, but the definition and pathogenesis of PNI in esophageal squamous cell carcinoma (ESCC) remains to be defined. PNI was evaluated by H&E staining and S100 immunohistochemistry. The predictive value of PNI in the prognosis of ESCC patients was analyzed. PNI was evaluated in vitro and in vivo. A total of 54 specimens (17.88%) were defined as PNI-a and 99 specimens (32.78%) as PNI-b. S100 staining was ...[more]
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Project description:BackgroundTumour perineural invasion (PNI) is a predictor of poor prognosis, but its effect on the prognosis of patients with colorectal cancer (CRC) has not yet been elucidated.MethodsThis retrospective study used propensity score matching (PSM). The clinical case data of 1470 patients with surgically treated stage I-IV CRC at Wuhan Union Hospital were collected. PSM was used to analyse and compare the clinicopathological characteristics, perioperative outcomes, and long-term prognostic outcomes of the PNI(+) and PNI(-) groups. The factors influencing prognosis were screened using Cox univariate and multivariate analyses.ResultsAfter PSM, 548 patients were included in the study (n = 274 in each group). Multifactorial analysis showed that neurological invasion was an independent prognostic factor affecting patients' OS and DFS (hazard ratio [HR], 1.881; 95% confidence interval [CI], 1.35-2.62; P = 0.0001; HR, 1.809; 95% CI, 1.353-2.419; P < 0.001). Compared to PNI(+) patients without chemotherapy, those who received chemotherapy had a significant improvement in OS (P < 0.01). The AUROC curve of OS in the PNI(+) subgroup (0.802) was higher than that after PSM (0.743), while that of DFS in the PNI(+) subgroup (0.746) was higher than that after PSM (0.706). The independent predictors of PNI(+) could better predict the prognosis and survival of patients with PNI(+).ConclusionsPNI significantly affects the long-term survival and prognosis of patients with CRC undergoing surgery and is an independent risk factor for OS and DFS in patients with CRC undergoing surgery. Postoperative chemotherapy significantly improved the OS of PNI(+) patients.
| S-EPMC10197328 | biostudies-literature
Project description:Perineural invasion (PNI) is one of the established prognostic factors in pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of PNI in patients with PDAC who received neoadjuvant therapy and pancreaticoduodenectomy is not clear. In this study, we performed a detailed examination of neural invasion in pancreaticoduodenectomy specimens from 212 patients with PDAC who received neoadjuvant chemoradiation (treated group) and in 60 untreated patients at our institution between January 1999 and December 2007. The frequency of PNI was higher in the untreated group (80%, 48/60) than in the treated group (58%, 123/212). For the 123 treated cases that were positive for PNI, extratumoral PNI, intratumoral PNI, intrapancreatic PNI only, extrapancreatic PNI, and intraneural invasion were identified in 86 (69.9%), 37 (30.1%), 11 (8.9%), 112 (91.1%), and 35 cases (28.5%), respectively. The presence of PNI correlated with tumor size, margin status, lymph node metastasis, pathologic tumor, and American Joint Committee on Cancer stages in the treated group. Tumor involvement of nerves >0.8 mm correlated with higher frequency of positive margin compared with tumors with PNI involving nerves ≤0.8 mm but not with other clinicopathologic parameters and survival. In the treated group, the presence of PNI or intraneural invasion correlated significantly with shorter disease-free survival and overall survival compared with no PNI or PNI only, respectively. PNI was an independent prognostic factor for both disease-free survival and overall survival in multivariate analysis. Our results showed that PNI plays an important role in the progression of PDAC and in predicting prognosis in this group of patients.
| S-EPMC3288807 | biostudies-literature
Project description:Previous studies have shown that the presence of perineural invasion (PNI) is associated with a significantly worse prognosis in colorectal cancer (CRC) patients. In this study, we performed a detailed analysis of the diversity of extracellular vesicles (EV) between NPNI (non-PNI) and PNI using quantitative proteomics and aim to investigate the mechanisms underlying PNI in colorectal cancer. Quantitative proteomics technology was used to identify the proteome of serum-purified EVs from CRC patients with and without PNI (PNI and non-PNI (NPNI) groups, respectively) and healthy volunteers. Mass spectrometry data were verified by ELISA and Western blot analyses. The proteomic profile of serum EVs from the PNI group differed from that of those in the NPNI group. Serum-derived EVs from the PNI promoted more significant cellular mobility than EVs derived from the NPNI group. EV stratifin (SFN) expression levels demonstrated an area under the receiver operating characteristic curve values of 0.84 for discriminating patients with PNI from NPNI patients. Moreover, EV SFN expression levels were an independent predictor of CRC prognosis. In this study, we identified SFN as a potential biomarker for the diagnosis of PNI in stage II CRC patients.
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Project description:Perineural invasion (PNI) is a mechanism of tumor dissemination that can provide a challenge to tumor eradication and that is correlated with poor survival. Squamous cell carcinoma, the most common type of head and neck cancer, has a high prevalence of PNI. This review provides an overview of clinical studies on the outcomes and factors associated with PNI in head and neck cancer and on findings on cancer-nerve crosstalk.
| S-EPMC6728584 | biostudies-other
Project description:BackgroundPerineural invasion (PNI) is regarded as a prognostic factor for patients with GC. However, the significance of PNI in patients with stage II GC remains unclear. This study aimed to investigate the clinical implication of PNI in patients with stage II GC undergoing curative resection.MethodsPatients with stage II GC who underwent curative resection were retrospectively evaluated from January 2010 to July 2019. According to PNI status, all patients were divided into two groups: with or without PNI. The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models.ResultsA total of 233 patients were included in this study. There were 100 patients with PNI (42.92%) and 133 patients without PNI (57.08%). The overall survival (OS) and disease-free survival (DFS) rates for patients with PNI were significantly lower than that for patients without PNI (p = 0.019 and p = 0.032, respectively). Multivariate analysis indicated that the presence of PNI was an independent risk factor for OS (hazard ratio (HR): 1.76, 95% confidence interval (CI) 1.02-3.06, p = 0.044) and DFS (HR: 1.70, 95% CI 1.04-2.80, p = 0.035), while adjuvant chemotherapy (AC) was an independent protective factor for OS (HR: 0.51, 95% CI 0.30-0.88, p = 0.016) and DFS (HR: 0.52, 95% CI 0.31-0.86, p = 0.011). Furthermore, among patients with PNI, those who received AC had better OS (p = 0.022) and DFS (p = 0.027) than their counterparts. When patients with PNI received AC, the OS (p = 0.603) and DFS (p = 0.745) appeared to be similar to those without PNI and no AC.ConclusionIn patients with stage II GC undergoing curative resection, the presence of PNI was associated with worse survival, which appeared to improve with the treatment of AC, indicating a potential need for more intensive AC.
| S-EPMC10685670 | biostudies-literature
Project description:Purpose: There is currently a lack of validated predictors for adjuvant chemotherapy efficacy in patients with gastric cancer (GC). Perineural invasion (PNI) is the process of neoplastic invasion of the nerves, accompanied by tumor microenvironment (TME) changes. TME can determine treatment outcome while the impact of PNI on chemotherapy efficacy remains unknown in GC. We investigated the association between PNI and the efficacy of postoperative adjuvant chemotherapy in patients with resected GC. Methods: Patients who underwent radical resection of stage IB-III GC with or without fluoropyrimidine (FU)-based adjuvant chemotherapy were retrospectively selected from two separate patient cohorts. PNI was confirmed with S100 immunohistochemistry (IHC). Tumor hypoxia and activity of selected pathways were quantified by mRNA-based signature scoring based on publicly available data. A hypoxia biomarker, ERO1A, and a FU resistance biomarker, thymidylate synthase (TS), were assessed by IHC, respectively. Results: Two cohorts included 223 and 599 patients, respectively. Adjuvant chemotherapy significantly improved overall survival (OS) and disease-free survival (DFS) in PNI-positive but not in PNI-negative patients, which was not impacted by stages. Multivariate models showed that adjuvant chemotherapy was an independent predictor for OS and DFS in PNI-positive patients in both cohorts. For TME, PNI-negative tumors were more hypoxic than were PNI-positive tumors, and displayed relative up-regulation of signaling along the pathways that are important in FU metabolism or resistance. Expressions of ERO1A and TS significantly decreased in PNI-positive compared to PNI-negative tumors. Conclusions: PNI might help predict adjuvant chemotherapy benefit in patients with resected GC. Validation in prospective studies is required. Novel treatment strategies need to be developed in PNI-negative patients.
| S-EPMC7186485 | biostudies-literature
Project description:Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13Rα2) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 -ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13Rα2 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.
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Project description:Perineural invasion (PNI) is an ominous form of cancer progression along nerves associated with poor clinical outcome. Glial derived neurotrophic factor (GDNF) interacts with cancer cell RET receptors to enable PNI, but downstream events remain undefined. We demonstrate that GDNF leads to early activation of the GTPase Cdc42 in pancreatic cancer cells, but only delayed activation of RhoA and does not affect Rac1. Depletion of Cdc42 impairs pancreatic cancer cell chemotaxis toward GDNF and nerves. An siRNA library of guanine nucleotide exchange factors was screened to identify activators of Cdc42. ARHGEF7 (?-Pix) was required for Cdc42 activation and chemotaxis toward nerves, and also colocalizes with RET under GDNF stimulation. Cdc42 enables PNI in an in vitro dorsal root ganglia coculture model, and controls the directionality of migration but does not affect cell speed or cell viability. In contrast, Rac1 was necessary for cell speed but not directionality, while the RhoA was not necessary for either cell speed or directionality. Cdc42 was required for PNI in an in vivo murine sciatic nerve model. Depletion of Cdc42 significantly diminished the length of PNI, volume of PNI, and motor nerve paralysis resulting from PNI. Activated Cdc42 is expressed in human salivary ductal cancer cells invading nerves. These findings establish the GDNF-RET-?-Pix-Cdc42 pathway as a directional regulator of pancreatic cancer cell migration toward nerves, highlight the importance of directional migration in PNI, and offer novel targets for therapy. IMPLICATIONS: Cdc42 regulates cancer cell directional migration toward and along nerves in PNI.
| S-EPMC7272295 | biostudies-literature
Project description:The invasion of nerves by cancer cells, or perineural invasion (PNI), is potentiated by the nerve microenvironment and is associated with adverse clinical outcomes. However, the cancer cell characteristics that enable PNI are poorly defined. Here, we generated cell lines enriched for a rapid neuroinvasive phenotype by serially passaging pancreatic cancer cells in a murine sciatic nerve model of PNI. Cancer cells isolated from the leading edge of nerve invasion showed a progressively increasing nerve invasion velocity with higher passage number. Transcriptome analysis revealed an upregulation of proteins involving the plasma membrane, cell leading edge, and cell movement in the leading neuroinvasive cells. Leading cells progressively became round and blebbed, lost focal adhesions and filipodia, and transitioned from a mesenchymal to amoeboid phenotype. Leading cells acquired an increased ability to migrate through microchannel constrictions and associated more with dorsal root ganglia than nonleading cells. ROCK inhibition reverted leading cells from an amoeboid to mesenchymal phenotype, reduced migration through microchannel constrictions, reduced neurite association, and reduced PNI in a murine sciatic nerve model. Cancer cells with rapid PNI exhibit an amoeboid phenotype, highlighting the plasticity of cancer migration mode in enabling rapid nerve invasion.
| S-EPMC10151474 | biostudies-literature
Project description:PurposePerineural invasion (PNI) is an adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OCSCC). The American Joint Committee on Cancer Staging Manual, eighth edition, introduced a subdivision of PNI into two distinct forms, that is, extratumoral and intratumoral PNI (EPNI and IPNI, respectively). We designed the current study to assess whether EPNI and IPNI have different prognostic implications in terms of disease control and survival outcomes in patients with OCSCC.Materials and methodsWe retrospectively examined 229 consecutive patients with OCSCC and PNI who underwent radical surgery between July 2003 and November 2016. EPNI and IPNI were identified in 76 and 153 patients, respectively. The 5-year locoregional control (LRC), distant metastasis, disease-free survival (DFS), and overall survival (OS) rates served as the main outcome measures.ResultsCompared with patients showing IPNI, those with EPNI had a higher prevalence of worst pattern of invasion type-5 (P < 0.001), alcohol consumption (P = 0.03), and close margins (P = 0.002). Univariate analysis revealed that EPNI was a significant predictor of 5-year LRC (P = 0.024), DFS (P = 0.007), and OS (P = 0.034) rates. After allowance for potential confounders in multivariable analysis, ENPI was retained in the model as an independent predictor of 5-year LRC (P = 0.028), DFS (P = 0.011), and OS (P = 0.034) rates.ConclusionCompared with IPNI, the presence of EPNI in OCSCC portends less favorable outcomes. Patients with EPNI are potential candidates for definite aggressive treatment modalities aimed at improving prognosis.
| S-EPMC6797567 | biostudies-literature