Prognostic Value of Perineural Invasion in Gastric Cancer: A Systematic Review and Meta-Analysis

Abstract

BackgroundThe prognostic role of perineural invasion in gastric cancer is controversial. Here, we present a systemic review and meta-analysis of the association between perineural invasion and survival in resectable gastric cancer patients.MethodsA comprehensive literature search for relevant reports published up to April 2013 was performed using PubMed, Embase, Web of Science and Wanfang Data. Studies that investigated the role of perineural invasion with a sample size greater than 100 were included and analyzed.ResultsA total of 30,590 gastric cancer patients who had undergone curative gastrectomy from twenty-four studies were included. The median rate of perineural invasion positive was 40.9% (6.8%–75.6%). Fourteen studies investigated overall survival unadjusted for other variables in 23,233 gastric cancer patients. The relative hazard estimates ranged from 0.568–7.901 with a combined random effects estimate of 2.261 (95% CI = 1.841–2.777, P = 0.000). The effect of perineural invasion on overall survival adjusted for other prognostic factors was reported in 17 studies incorporating 8,551 cases. The hazard estimates ranged from 0.420–8.110 with a pooled random effects estimates of 1.484 (95% CI = 1.237–1.781, P = 0.000). There was heterogeneity between the studies (Q = 49.22, I-squared = 67.5%, P = 0.000). Disease-free survival was investigated adjusted in four studies incorporating 9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CI = 1.230–1.527, P = 0.000).ConclusionPerineural invasion is an independent prognostic factor affecting overall survival and disease-free survival of gastric cancer patients who had undergone the curative resection. This effect is independent of lymph node status, tumor size and the depth of invasion as well as a range of other biological variables on multivariate analysis. Large prospective studies are now needed to establish perineural invasion as an independent prognostic marker for gastric cancer.

Prognostic Significance of Metastatic Lymph Node Ratio in Gastric Cancer

“…Our study found a significant correlation between LNR and lymphovascular invasion and perineural invasion. Deng et al and Li et al have in their study concluded that LVI and PNI are independent prognostic factors in gastric carcinoma [9,10]. In the current study, LVI (p<0.05) and PNI (p<0.05) were found to have a significant statistical correlation with LNR.…”

Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma

“…There are clinical and prognostic indicators that have a well-known prognostic value, including LVI, PNI, and the disease stage in gastric cancer (18)(19)(20). In the current study, these indicators were evaluated in the two groups, and patients with AFP-SGC were revealed to be diagnosed at more advanced stages, and to have more LVI and PNI compared with the non-AFP-SGC group.…”

Complexity of Neural Component of Tumor Microenvironment in Prostate Cancer

“…Neural microenvironment and cancer-related axonogenesis constitute new fields for investigation that require further exploration in PC and other neoplasms [18][19][20][21][22][25][26][27][28][29]. Future studies are needed to advance current understanding of molecular mechanism and neural signaling pathways that mediate neoneurogenesis and their impact on cancer development and progression.…”

“…PNI occurs in many tumors being common pathological finding in gastrointenstinal tract tumors, as in pancreatic carcinoma it reaches even 100% [67]. A metaanalysis of 24 studies on the incidence and prognostic significance of PNI in gastric cancer showed its 6.8-75.6% occurrence and confirmed its impact on the overall survival rate [28]. In head and neck squamous cell carcinomas, PNI is reported in 25-80% of cases with relation to worse prognosis and increased risk of regional recurrences.…”

“…PNI is not only the form of tumor infiltration but it also creates the neural TME and tumor promoting perineural niche [25]. The occurrence of PNI was found to be factor indicating poor prognosis correlated with decreased overall and diseasefree survival time in many cancers including prostatic, colon, pancreatic, gastric and head and neck carcinoma [26][27][28][29].…”