A Comprehensive Study of Extramural Venous Invasion in Colorectal Cancer

Abstract

Colorectal cancer is a common malignancy and a leading cause of cancer related death. Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease. In colorectal cancer, tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome. Increasing emphasis is now being placed on other factors, especially the presence of extramural venous invasion (EMVI). It is important to understand the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance. This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre, using prospectively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period. Overall, EMVI was reported in 27.9% of colorectal cancer excision specimens. In tumours (n = 1928) that had not received neoadjuvant therapy, the presence of EMVI varied significantly depending on tumour site (χ2 = 12.03, p<0.005), tumour stage (χ2 = 268.188, p<0.001), lymph node stage (χ2 = 294.368, p<0.001) and Dukes' stage (χ2 = 253.753, p<0.001). Multivariate analysis confirmed EMVI as a significant independent prognostic indicator (p<0.001). In conclusion, the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors. This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also understanding the relationship of EMVI with other prognostic factors.

Conflict of interest statement

Competing Interests: GIM is a scientific advisor to Vertebrate Antibodies. DM declares no competing interest. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. EMVI in colorectal cancer.

(A) Haematoxylin and eosin. (B) Elastic haematoxylin and eosin.

Fig 2. Frequency of EMVI in relation to site of primary tumour.

(A) All cases. (B) Cases that had not received neoadjuvant therapy. (C) Cases that had received neoadjuvant therapy. (D) Non-screen-detected cases. (E) Bowel cancer screening detected cases.

Fig 3. Frequency of EMVI reporting per tumour (T) stage of primary tumour.

(A) All cases. (B) Cases that had not received neoadjuvant therapy. (C) Cases that had received neoadjuvant therapy. (D) Non-screen-detected cases. (E) Bowel cancer screening detected cases. T0 represents cases in which there was a complete pathological response of the primary tumour to neoadjuvant therapy.

Fig 4. Frequency of EMVI reporting per lymph node (N) stage of primary tumour.

(A) All cases. (B) Cases that had not received neoadjuvant therapy. (C) Cases that had received neoadjuvant therapy. (D) Non-screen-detected cases. (E) Bowel cancer screening detected cases.

Fig 5. Frequency of EMVI reporting per Dukes’ stage of primary tumour.

(A) All cases. (B) Cases that had not received neoadjuvant therapy. (C) Cases that had received neoadjuvant therapy. (D) Non-screen-detected cases. (E) Bowel cancer screening detected cases.

Fig 6. Relationship between extramural venous invasion and survival.

(A) All patients (n = 1004). (B) Patients who did not receive neoadjuvant therapy (n = 731). (C) Patients who received neoadjuvant therapy (n = 273). (D) Colon cancer cases that did not receive neoadjuvant therapy (n = 653). (E) All rectal cancer cases (n = 396). (F) Rectal cancer cases that received neoadjuvant therapy (n = 318). (G) Rectal cancer cases that did not receive neoadjuvant therapy (n = 78).

Fig 7. Relationship between extramural venous invasion and survival in Dukes’ B cancers.

(A) All patients (n = 372). (B) Patients who did not receive neoadjuvant therapy (n = 301). (C) Patients who received neoadjuvant therapy (n = 71).

Fig 8. Relationship between extramural venous invasion and survival in Dukes’ C cancers.

(A) All patients (n = 390). (B) Patients who did not receive neoadjuvant therapy (n = 319). (C) Patients who received neoadjuvant therapy (n = 71).

Fig 9. Relationship between extramural venous invasion and survival and screening in colorectal cancers.

(A) All non-screen detected cancer patients (n = 879). (B) Non-screen-detected cancer patients who did not receive neoadjuvant therapy (n = 638). (C) Non-screen-detected cancer patients who received neoadjuvant therapy (n = 241). (D) All bowel cancer screening detected cases (n = 125). (E) Bowel cancer screening detected patients who did not receive neoadjuvant therapy (n = 93).