Immunohistochemical Assessment of Lymphovascular Invasion in Stage I Colorectal Carcinoma

Abstract

Several studies have suggested that the presence of occult nodal metastases (micrometastases) is related to adverse clinical course in stage I colorectal carcinoma. Herein we analyzed the correlation between nodal micrometastases and lymphovascular invasion (LVI) or lymphatic vessel density (LVD) in a series of stage I colorectal carcinomas; the cohort included cases characterized or not characterized by disease progression during the follow-up. In these cases, LVI and LVD were evidenced through the immunohistochemical detection of the specific marker for lymphatic vessels, D2-40. LVI was significantly more frequent in colorectal carcinomas characterized by the presence of micrometastases (P<0.0001), high peritumoral LVD (P<0.0001), and disease progression (P<0.0001). The analysis for progression risk indicated that nodal micrometastases and LVI were significant, negative, independent prognostic parameters associated with shorter disease-free survival of stage I colorectal cancer (P=0.0001; P=0.0242). In conclusion, in this study we demonstrated for the first time that LVI is significantly associated with nodal occult metastases in stage I colorectal carcinoma. In the light of its significant, independent, prognostic value in this neoplasia, the detection of LVI may represent a faster and cheaper tool compared with the time-consuming evaluation of micrometastases to select high-risk patients who may benefit from adjuvant systemic treatment. Furthermore, the assessment of LVI may be applied to establish the likelihood of nodal involvement from carcinomas treated with conservative local excision techniques, which provide no regional nodes for histologic examination.

Quantification of tumour budding, lymphatic vessel density and invasion through image analysis in colorectal cancer

“…This, alongside no standardised reporting methodology, is another contributing factor for the absence of lymphatic vascular based prognostic features from the minimal core data set and so standard practice is to not report LVI or LVD in the clinic. To overcome the problem of identifying LVI, studies have employed immunohistochemical staining with a D2-40 antibody which specifically binds to lymphatic vessel endothelial cells [22,28]. Dual staining of epithelium and vessels allows easier recognition and reporting of LVI events [28] within the complex tumour microenvironment while automated quantification adds further robustness to the data.…”

“…Dual staining of epithelium and vessels allows easier recognition and reporting of LVI events [28] within the complex tumour microenvironment while automated quantification adds further robustness to the data. LVI alone has been associated with lymph node metastasis (LNM) and poor outcome [22,29]. The under-recognition of LVI may be a contributing factor for the under-staging of CRC patients [22,27] and disease recurrence in ~30% of the Dukes B population [4,37].…”

“…A number of these have concentrated on early stage disease and the ability to utilise histopathological features to predict lymph node metastasis or to stratify patients at high risk of disease recurrence and poor outcome [6,9,16,18-22]. Although LVI and TB have been shown to be significantly prognostic in most of these studies they are not, along with LVD, routinely reported in the clinical pathology report and are not included within the minimum core data set compiled by the Royal College of Pathologists [1], wherein only TB is listed as a non-core data item.…”

“…In fact lymphatic vessels, unlike blood vessels, are especially difficult to observe in H&E stained tissue sections where they may be confused with retraction artefact. Specific stains are more frequently being employed [9,22,26,28-30] in order to increase reporting rate and decrease observer variability but there is no consensus yet on what is best. Thus the manual, semi-quantitative scoring employed in these studies is subjective, open to variability and time consuming.…”

Association between raf kinase inhibitor protein loss and prognosis in cancers of the digestive system: A meta-analysis

“…However, due to the high malignant po-tential of digestive system cancers, they are usually diagnosed at an advanced stage and often recur even after curative surgical excision. Conventional prognostic factors such as tumor stage, grade and size et al do not accurately predict the clinical outcome of many patients with gastrointestinal cancers, and widespread efforts have been made to identify markers that predict recurrence and progression of the disease, response to treatment, and survival [7][8][9][10][11].…”