Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.
BACKGROUND
Both dermal and ocular melanocytic nevi have been reported to undergo changes during pregnancy. This has been proposed to be related to hormonal influences; however, few studies have provided any proof. We therefore set out to evaluate the expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.


METHODS
Formalin-fixed, paraffin-embedded material from 76 tumors--69 conjunctival nevi, 5 specimens of primary acquired melanosis (PAM), and 2 conjunctival melanomas--were included in a tissue microarray (TMA) format. The TMA sections were analyzed by immunohistochemistry with antibodies for progesterone and estrogen receptors, and cell cycle-related proteins (p16, MIB1-Ki67).


RESULTS
Progesterone receptors were highly (96%) and similarly expressed in all lesions. In addition, progesterone receptor expression showed a tendency to increase with age (p=0.06). In contrast, estrogen receptor expression was completely absent in all tumors. The cell cycle regulator p16 was expressed in 97% of the lesions. The proliferation marker MIB1-Ki67 was expressed at low levels (mean+/-SD: 13+/-14%) in 79% of the lesions. No differences of expression were found between the different lesions and nevi types. The mean age of the patients was highest in conjunctival melanoma (70+/-22 years), followed by PAM (60+/-19 years) and nevi (36+/-18 SD years). The different types of nevi also showed significant age dependency (junctional 25+/-17 years, compound 34+/-17 years, dermal 49+/-15 years).


CONCLUSIONS
Our findings reveal the expression of progesterone, but not estrogen, in melanocytic lesions of the ocular conjunctiva. In benign conjunctival lesions, p16 and MIB1-Ki67 expression was comparable to that in benign nevi of the skin.
University Eye Clinic Freiburg, 79106 Freiburg, Germany. pache@aug.ukl.uni-freiburg.de
Mona
M
Pache
Katharina
K
Glatz-Krieger
Guido
G
Sauter
Peter
P
Meyer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003230:Conjunctival Neoplasms / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008548:Melanosis / Q000378:metabolism; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone