Glutathione S-transferase pi is expressed in (pre) neoplastic lesions of the human uterine cervix irrespective of their degree of severity.
BACKGROUND
Glutathione S-transferase pi (GST pi) is involved in a variety of cell detoxification processes. In the uterine cervix its presence has been associated with high grade cervical intraepithelial neoplasia (CIN), but the reports are conflicting. For this reason we immunohistochemically investigated glutathione S-transferase pi expression in a well documented sequence leading to cervical cancer.


METHODS
The series of tissue samples that were examined comprised normal, metaplastic, dysplastic (CIN 1, 11 and 111) and malignant cervix. GST pi expression was examined in 15 cases of uterine cervix lined with normal epithelia, in 11 cases of CIN 1, 9 cases of CIN 11, 10 cases of CIN 111, 6-cases of squamous cell cervical carcinomas and 5 cases of adenocarcinoma of the cervix.


RESULTS
Both nuclear and cytoplasmic staining reactions were noted. In normal ectocervical epithelia a moderately strong nuclear and cytoplasmic staining reaction was noted, while in immature squamous metaplasia staining was more intense. Only 50% of the endocervical cells were immunostained while almost 100% of the reserve cells stained weakly, mainly restricted to the cytoplasm. Irrespective of severity, CIN lesions showed a moderate staining intensity in both cytoplasm and nuclei. Cervical carcinoma, irrespective of their type, showed significantly less staining activity.


CONCLUSIONS
GST pi occurs in normal cervical epithelium and in all stages of premalignant cervix, suggesting an important role in the detoxification process in all these stages. Its ubiquitous presence indicates, in contrast to the earlier reports, that the enzyme does not play a crucial role in the initiation of the carcinogenic cascade. However, the absence of this detoxificating enzyme in the nucleus of the majority of cervical carcinomas may indicate that xenobiotic compounds are not catabolized and may therefore exert their mutagenic activity, resulting in tumor progression.
Martens
J E
JE
Department of Obstetrics and Gynecology, University Hospital of Rotterdam, The Netherlands.
Smedts
F
F
ter Harmsel
B
B
Helmerhorst
T J
TJ
Ramaekers
F C
FC
D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology; D002584:Cervix Uteri / Q000201:enzymology* / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology / Q000473:pathology; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007044:Hysterectomy; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008679:Metaplasia; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery
D007527:Isoenzymes; D005982:Glutathione Transferase