Faculty Bibliography

The purpose of this study was to correlate the presence of matrix metalloproteinase (MMP)-9 and MMP-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 mRNAs, detected in serial sections using the reverse transcriptase in situ PCR technique, with prognosis in 23 cases of cervical carcinoma. PCR-amplified MMP and TIMP cDNA were restricted to the invasive cancers cells and the surrounding stromal cells. The ratios of cancer and stromal cells expressing MMP-9 and MMP-2 to those expressing TIMP-1 and TIMP-2 were approximately 1 in those cancers with a good prognosis. This MMP:TIMP ratio in the cancer and stromal cells with a poor prognosis was significantly increased to 5.4 and 3.4 (P < 0.0001), respectively, reflecting a marked reduction in the TIMP detection rate in cancers with a poor prognosis. In cervical cancer cell lines SiHa and HeLa, the MMP:TIMP ratio was also close to 1 and, interestingly, these cell lines are invasive but rarely metastatic in nude mice. These data suggest that the balance of MMP-9 and MMP-2 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of cervical cancer

The purpose of this study was to determine the histological distribution of in situ polymerase chain reaction (PCR)-amplified HIV-1 nucleic acids in the male genital tract to elucidate the mechanism of sexual transmission of AIDS. Viral DNA was detected in the testicular tissue of 11 of 12 men with HIV-1 infection using the PCR in situ hybridization technique. The amplified viral DNA localized to many spermatogonia, spermatocytes, and rare spermatids. Relatively few viral infected macrophages were noted, mostly in the prostate. The viral infection was activated given the presence of cDNA sequences consistent with genomic and multiple spliced transcripts as determined by reverse transcription in situ PCR. PCR-amplified viral nucleic acids were not detected in the epithelial of the prostate, epididymis, seminal vesicles, or penis in men with AIDS nor in any genital tract tissues from three boys who died of AIDS acquired in utero. The demonstration that HIV-1 selectively infects the spermatogonia and their progeny suggests that this may serve as a primary source of venereal spread of the virus. Concomitant destruction of these cells by HIV-1 may also explain the marked inhibition of spermatogenesis and severe atrophy that characterizes the testes in AIDS