Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance

Wang, Hao; Huo, Ruixue; He, Kexin; Cheng, Li; Zhang, Shan; Yu, Minhao; Zhao, Wei; Li, Hui; Xue, Junli

doi:10.1007/s13402-023-00857-y

Cited by 20 publications

(4 citation statements)

References 196 publications

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“…Neural invasion refers to tumor cells invading the nerve sheath or the presence of tumor cells within the nerve sheath, which is associated with tumor invasion, metastasis, cancer-related pain, and poor clinical outcomes. The New England Journal of Medicine has also considered neural invasion as pathological evidence of early metastasis in colorectal cancer, being independently associated with low survival rates ( 20 ). This study confirmed that TNM stage III and neural invasion are independent risk factors for DFS in patients after radical rectal cancer surgery, and incorporated them into the predictive model.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a nomogram for predicting disease-free survival after radical resection of rectal cancer using perioperative inflammatory indicators

Sun,

Zhong,

Yin

et al. 2024

J Gastrointest Oncol

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Background Colorectal cancer is a common digestive tract malignancy that seriously affects patients’ quality of life and survival time. Surgery is the main treatment modality, but postoperative prognosis varies greatly. This study sought to explore the impact of perioperative inflammatory indicators on disease-free survival (DFS) in patients after radical resection of rectal cancer and to construct a nomogram for clinical reference. Methods A retrospective analysis was performed on 304 primary rectal adenocarcinoma patients who underwent laparoscopic radical resection of rectal cancer at the Affiliated Hospital of Xuzhou Medical University from May 1, 2018 to September 30, 2020. The patients were divided into a training set (n=213) and a validation set (n=91) at a ratio of 7:3. The cut-off values of each inflammatory indicator based on the receiver operating characteristic (ROC) curve were determined and each indicator was divided into high and low groups. The least absolute shrinkage and selection operator (LASSO)-Cox regression model was used to analyze the independent risk factors affecting DFS, and a nomogram was established. The model was internally validated using the validation set, and the discrimination, calibration, and clinical application value of the nomogram were evaluated using ROC curve, calibration curve, and clinical decision curve analysis (DCA). Results Tumor-node-metastasis (TNM) stage III, neural invasion, preoperative neutrophil-to-lymphocyte ratio (NLR) ≥1.995, postoperative systemic immune-inflammation index (SII) ≥451.05, and Δpan-immune-inflammation value (ΔPIV) ≥144.36 (P<0.05) were independent factors for predicting the 3-year DFS of patients after rectal cancer surgery. The area under the ROC curve (AUC) of the nomogram was 0.811 [95% confidence interval (CI): 0.778–0.889] in the training set and 0.808 (95% CI: 0.785–0.942) in the validation set. The nomogram showed good calibration, indicating good consistency between predicted and actual risks. DCA demonstrated the clinical utility of the nomogram. Conclusions The nomogram constructed based on TNM stage III, neural invasion, preoperative NLR ≥1.995, postoperative SII ≥451.05, and ΔPIV ≥144.36 can predict the risk of 3-year DFS in patients undergoing curative surgery for rectal cancer, enabling strict postoperative follow-up and timely adjuvant treatment for high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Construction and validation of a nomogram for predicting disease-free survival after radical resection of rectal cancer using perioperative inflammatory indicators

Sun,

Zhong,

Yin

et al. 2024

J Gastrointest Oncol

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“…In addition, in our study, perineural invasion frequency was higher in the rsCRC group, which might explain the lower survival and higher mortality reported. Many studies reported a significant association between perineural invasion and bad CRC prognosis and outcome, including higher recurrence, lower DFS, and OS, requiring adjuvant therapy [ 28 ]. Though no reports in the literature described specifically the perineural invasion status in the rsCRCs versus ocCRCs, perineural invasion reports are higher in rectal cancer compared to colon cancer and reflect a bad prognosis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Differences in Clinicopathological Features, P16Ink4a and P57KIP2 Immunohistochemical Expressions, and Survival Between Colorectal Carcinoma in Rectosigmoid and Other Colonic Locations

Elkhamisy,

Aboelkomsan,

Foda

2024

Cureus

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Background One unique criterion of colorectal carcinoma (CRC) is the different locations within the colorectum. Different CRC sidedness/locations could have distinct criteria, including risk factors, morphological features, genetic alterations, prognostic factors, and clinical outcomes. Nearly half of the CRC cases occur in the rectal-sigmoid locations, while other colonic locations constitute the other half. Investigating specific protein expression patterns in the rectosigmoid CRC (rsCRC) compared to other colonic (ocCRC) locations helps understand the disease pathogenesis, predict prognosis, and design personalized treatments. This study is the first to compare P16Ink4a and P57KIP2 immunohistochemical (IHC) expression in rsCRC to ocCRC and examine their relationship to disease outcomes in both locations. Materials and methods A comparative cross-sectional study used tissue microarray slides from rsCRC and ocCRC that were immunohistochemically stained by anti-P16Ink4a and P57KIP2 antibodies. A semi-quantitative scoring system classified each marker's expression as positive or negative. The statistical analysis compared clinicopathological features, P16Ink4a and P57KIP2 expressions, and their relationship to clinical outcomes in rsCRC and ocCRC cases. Results One hundred fifty CRCs were distributed into the rsCRC cases (n=86, 57.3%) and the ocCRC cases (n=64, 42.7%). The rsCRC cases had a significantly lower age <40 years (P=0.002), higher frequency of mismatch repair (MMR) proficient status (P=0.003), and perineural invasion (P=0.008), with lower disease-free (DFS) and overall survival (OS) (P=0.03, and P=0.015, respectively). Significantly higher positive P16Ink4a and P57KIP2 IHC expressions were found in the rsCRCs compared to the ocCRCs (P=0.02, and P=0.03, respectively); however, their relationship to the hazards (HR) of recurrence (HR=4.02, P=0.058, and HR=0.36, P=0.14, respectively) and mortality (HR=2.56, P=0.21, and HR=0.23, P=0.58, respectively) in the rsCRC group was statistically nonsignificant. In the ocCRC group, P16Ink4a positivity was significantly associated with a higher disease recurrence and mortality hazard (HR=8.19, P=0.007, and HR=5.57, P=0.037, respectively), while P57KIP2 positivity was significantly associated with a lower mortality hazard (HR=0.12, P=0.027). Conclusion The rsCRCs differ from ocCRCs in clinicopathological criteria and protein expression patterns. Though P16Ink4a and P57KIP2 IHC expressions are higher in the rsCRC than in the ocCRC, their value as outcome predictors is higher in the ocCRCs rather than the rsCRCs. P16Ink4a and P57KIP2 can act as prognostic markers and be suitable targets for therapy modulation in the ocCRC group.

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“…Perineural invasion (PNI) is a common pathological feature found in cancers of nerverich regions, such as prostate cancer, pancreatic cancer, and head and neck cancers [40]. PNI has long been a focus of research because it is considered a route of metastasis in addition to the vascular and lymphatic channels, and multiple studies have associated PNI with an unfavorable prognosis [40][41][42][43]. In this chapter, the main features and mechanisms of PNI are presented, and the limitations in diagnosis are also discussed.…”

Section: Perineural Invasionmentioning

confidence: 99%

Tumor Neurobiology in the Pathogenesis and Therapy of Head and Neck Cancer

Liang,

Hess

2024

Cells

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The neurobiology of tumors has attracted considerable interest from clinicians and scientists and has become a multidisciplinary area of research. Neural components not only interact with tumor cells but also influence other elements within the TME, such as immune cells and vascular components, forming a polygonal relationship to synergistically facilitate tumor growth and progression. This review comprehensively summarizes the current state of the knowledge on nerve–tumor crosstalk in head and neck cancer and discusses the potential underlying mechanisms. Several mechanisms facilitating nerve–tumor crosstalk are covered, such as perineural invasion, axonogenesis, neurogenesis, neural reprogramming, and transdifferentiation, and the reciprocal interactions between the nervous and immune systems in the TME are also discussed in this review. Further understanding of the nerve–tumor crosstalk in the TME of head and neck cancer may provide new nerve-targeted treatment options and help improve clinical outcomes for patients.

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Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance

Cited by 20 publications

References 196 publications

Construction and validation of a nomogram for predicting disease-free survival after radical resection of rectal cancer using perioperative inflammatory indicators

Construction and validation of a nomogram for predicting disease-free survival after radical resection of rectal cancer using perioperative inflammatory indicators

Differences in Clinicopathological Features, P16Ink4a and P57KIP2 Immunohistochemical Expressions, and Survival Between Colorectal Carcinoma in Rectosigmoid and Other Colonic Locations

Tumor Neurobiology in the Pathogenesis and Therapy of Head and Neck Cancer

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