Metastasis is fundamentally an embolic process. It may be viewed as a series of events that occur sequentially, with invasion of lymphovascular channels as an important early stage. Once the malignant cells have accessed the lymphovascular space they can grow along the lumen and permeate the lymphatic drainage in that area, or disseminate more widely. Therefore, LVSI has been regarded as an important predictive factor of nodal metastases and recurrent disease in various solid tumours.4,5
“We noted a significant rise amounting to a threefold increase in the detection rate of lymphovascular space invasion by using the dual immunostaining technique”
Ours is the first study to report the use of dual immunostaining to identify tumour cells within the lymphovascular space using pancytokeratin and endothelial cell markers. There have been many attempts in the past to improve the detection rate of LVSI. Single immunostaining for factors including factor VIII, CD31, and podoplanin have all led to an increase in the detection rate of LVSI, but have failed to reach significance.6–8
In addition, combinations of the above factors have also been used to improve the detection of LVSI and to distinguish lymphatic from blood vessel invasion. In cervical carcinoma, Birner et al
reported an LVSI detection rate of 47% (46 of 98) using both factor VIII and podoplanin immunostaining. However, the detection rate (47% v
34%) was not significantly different from that with H&E staining.8
More specifically, in endometrial cancer immunostaining with antibodies for von Willebrand factor and blood group isoantigens was used by Tsuruchi et al
They similarly reported no significant increase in the detection rate in comparison with conventional H&E. In only two of 62 of their cases where H&E had failed to detect LVSI did IHC positively identify LVSI. In contrast, in our study we noted a significant rise amounting to a threefold increase in the detection rate of LVSI (54% v
18%) by using the dual immunostaining technique (p < 0.001). Although this increased detection rate establishes the improved sensitivity of IHC over H&E staining in the detection of LVSI, further studies are needed to establish the clinical relevance of this finding. The high percentage of LVSI detected by this technique suggests that it may be overly sensitive in picking up either very low levels of circulating tumour cells or those that are carried over into vascular spaces during specimen handling and sectioning, neither of which may have the same adverse implications as LVSI detected by conventional methods. Certainly, the technique is recommended for identifying cases of LVSI that are doubtful on H&E staining.
We hope that these preliminary results will encourage further application of this inexpensive, readily available technique on other solid tumours to corroborate the clinical value of LVSI.