Losses of expression of the antigens A, Lea and Lex and over-expression of Ley in carcinomas and HG-SIL of the uterine cervix

Abstract

Background: The glycosylation of a great number of molecules, glyco-protein or glycolipids, has been of interest for decades.

Objective: To compare the expressive patterns of the isoantigenic determinants of histo-blood groups ABH and Lewis in squamous and simple epithelium and in precursors and cancers of the cervix.

Methods: A total of 36 lesions and neoplasms (10 LG-SIL, 16 HG-SIL and 10 invasive carcinomas) have been studied with immunohistochemical techniques, using monoclonal antibodies (MoAb BG1 to BG8) for precursor chains, blood-group ABH and Lewis group Le(a), Le(b), Le(x), and Le(y), and four types of lectins. In addition, we have studied the expression of p53 protein and PCNA, establishing the rate of proliferation of each lesion. Using PCR techniques, we have also detected part of the intron of the E6 gene of HPV-16.

Results: In the invasive cervical carcinomas, we observed a loss of expression of the Le(x) antigen (p < 0.01). With regard to the progression of the different lesions studied, we found alterations in the patterns of expression of the antigens of the ABH and Lewis blood groups. There was a tendency towards a loss of expression and heterogeneous patterns in the more advanced lesions, as well as over-expression of the Le(y) antigens. With PCNA, we established a proliferative rate which tended to be greater in relation to the progression of the cervix neoplasms.

Conclusion: These results indicate that there is a relation between the losses of histo-blood groups and the progression of the squamous intraepithelial lesions.

Figure 1

PCR – Dot-blotting. Results of the amplification from intro E6 of the HPV-16 and its specific hibridization.

Figure 2

Summary of the staining profiles for anti-blood group monoclonal antibodies of the areas of cervical mature metaplasia, LG-SIL, HG-SIL and carcinomas. White areas indicate negative staining in the epithelium; dotted areas, positive staining and the localization of the staining in the epithelium. S: Simple endocervical epithelium, G: Pseudoglandular epithelium, E: Squamous exocervical epithelium, M: Mature metaplasias, LG: LG-SIL, HG:HG-SIL, I: Invasive Carcinomas. Diamon: Mucinous stain. Cilia: Cilia stain. Singel dot: ocassional positive cells.

Figure 3

Detail of the ciliary expression of MoAb BG1 (T1-CH).

Figure 4

Up: Squamous intraepithelial lesion of low grade (Condyloma). Expression of MoAb BG6 (Le^b) over the basal layer. Down: Squamous intraepithelial lesion of low degree (Flat condyloma). Uniform expression of MoAb BG2 (A) over the basal layer that is negative.

Figure 5

Up: CIN I with morphologic changes related to infection by HPV. Absence of expression of the MoAb BG2 (A) in the basal and parabasal layers, and expressión of this one Ab in the middle of epitelium. Down: Squamous intrapithelial lesion of the high grade. Area of heterogenous expression of MoAb BG6 (Le^b) in a CIN III. Focal losses of expression.

Figure 6

Up: Extension of CIN III in the pseudoglands that show a cellularity with heterogenous expression and diminution of the expression of MoAb BG2 (Blood Group A). Down: Detail of the same lesion where an abrupt cut of expression of MoAb BG2 is observed. In addition the expression of this Ab in the endothelial lining of small capillares can be appreciated like internal control.

Figure 7

Up: Pseudoglandular endocervical with positive expression for BG5 (Le^a) and CIN III invasion with lossess of peripheral expression of the same Ab. Down: The same cut with positive expression for PCNA in a 85% of cellularity, preferably in the periphery where the BG5 (Le^a) was not expressed.

Figure 8

Expression of PCNA in a 100% of the cellularity of an invading squamous carcinoma.