Immunocytochemistry Of Rectal Cancer Circumferential Margins In The Assessment Of Micrometastatic Disease

Abstract

Summary
Introduction - Micrometastatic disease has been shown in the literature to exist in the lymph nodes, peripheral circulation and bone marrow of colorectal cancer patients. Furthermore, micrometastatic disease has been shown to be associated with recurrence of the disease. However, there is no evidence of investigation into the micrometastastic disease at the circumferential margins of rectal cancers. Therefore, this study was aimed at the assessment of micrometastatic disease in the mesorectum and circumferential margins of rectal cancers.

Methods - Data on rectal cancer patients who had a mesorectal excision with a curative intention were extracted from patient case notes. This included clinico- pathological information including recurrence and mortality related to cancer. All palliative resections, laparoscopic resections, polyp cancers and non-cancer mortality cases were excluded. We then retrospectively analysed rectal cancer specimens for the presence of micrometastasis (MM) and isolated tumour cells (ITC) in the mesorectum and at the circumferential margins by using automated immunocytochemistry (ICH) with MNF116 and CK5D3 monoclonal antibodies.The International Union Against Cancer (IUAC) criteria were applied objectively to classify the micrometastatic disease in to MM and ITC. This was compared with Haematoxylin and Eosin (H&E) staining method to assess any difference in the rate of detection of MM and ITC. An association of Micrometastatic disease with local recurrence and survival was studied.

Results - Immunocytochemistry was superior in the detection of ITC in the mesorectum compared with H&E staining (p=0.05) with a non-significant improvement in the detection of MM and ITC at the CRM using ICH. ITCs in the mesorectum and at the CRM were significantly associated with tumours larger than 4 cms in size. MM in the mesorectum was significantly associated with tumours with vascular invasion (p=0.000), lymph nodal involvement (p=0.004), Dukes stage (p=0.001), and nodal stage p= (0.000). Systemic recurrence was associated with MM (p=0.001) and ITC (p=0.001) at the CRM and MM in the mesorectum (p=0.05), but not by the ITC in the mesorectum (p=0.97). Interestingly, local recurrence was neither influenced by ITCs in the mesorectum (p=0.66) or CRM (p=0.66), nor by the MM in the mesorectum (p=0.66) or CRM (p=0.66). However, mesorectal MM (p=0.003), MM at the CRM (p=0.04), and ITC at the CRM (p=0.003) significantly affected the survival.

Conclusions - We have demonstrated the existence of micrometastases and isolated tumour cells at the circumferential margins and in the mesorectum of rectal cancers both by ICH and H&E. The immunocytochemistry was superior in the detection of both MM and ITC compared to H&E. Furthermore, MM and ITC have been shown to be associated with systemic recurrence of the disease and reduced survival. Potential implication of this of this research is that the use of adjuvant therapy may be extended in patients who are positive for micrometastatic disease at the circumferential margins and the mesorectum on immunocytochemistry to improve survival. Furthermore, it can be concluded that the immunocytochemistry may be applied routinely in the assessment of micrometastatic disease of rectal cancer circumferential margins.

Date of Award	Apr 2006
Original language	English
Supervisor	Jamal Ameen (Supervisor) & Anne-Marie Coll (Supervisor)