Clinical Significance of Distinguishing Homozygous from Heterozygous Complete Hydatidiform Mole
ME Klein, JD Pfeifer, BA Zehnbauer, AL Stephens, PC Huettner. Washington University Medical Center, St. Louis, MO
Background: Complete moles (CM) are abnormal conceptions composed entirely of paternal genetic material. About 80% are homozygous (HoCM) resulting from fertilization of an empty egg by one sperm with duplication of genetic material, while about 20% are heterozygous (HeCM) resulting from fertilization by two sperm. The literature suggests that HeCM may have a more aggressive course. We used multiplex PCR of short tandem repeats (STRs) at the CODIS loci to evaluate the accuracy of morphologic diagnosis of CM, to distinguish between HeCM and HoCM, and to investigate their clinical differences.
Design: Slides were reviewed from all consecutive, in-house cases of CM diagnosed on routine H&E at our institution between 1991 and 2007. DNA from maternal tissue (decidua) and villi was isolated by micro-dissecting unstained sections of formalin fixed paraffin embedded tissue. STR alleles at the CODIS loci, known to be highly polymorphic, were analyzed by multiplex PCR to distinguish HoCM from HeCM. Clinical data, including hCG levels, adverse outcomes such as invasive mole and pulmonary metastases, and use of chemotherapy, were obtained from chart review.
Results: To date we have analyzed 40 cases, of which 35 had adequate DNA. In each case, molecular analysis of villous tissue showed a diploid karyotype with absence of maternal alleles, confirming the diagnosis of CM. Thirty-one cases (88.6%) were HoCM and 4 (11.4%) were HeCM. Mean peak hCG levels were 523,499 Iu/L for HoCM and 322,193 Iu/L for HeCM. Complete follow up data were available for 17 patients with HoCM and 2 patients with HeCM. Mean time for hCG to return to normal was 9.8 wks (HoCM) and 12 wks (HeCM). Seven of 17 (41.2%) HoCM required chemotherapy (mean duration: 9.9 weeks), compared with one of two (50%) HeCM (duration: 10 weeks). Three of 17 (17.6%) HoCM had invasive mole and/or pulmonary metastases and one of two (50%) HeCM had pulmonary metastases. No patients developed choriocarcinoma.
Conclusions: Multiplex PCR of STRs at the CODIS loci confirmed the morphologic diagnosis of CM, and differentiated HoCM from HeCM, in all cases analyzed. While peak hCG levels were lower in HeCM than HoCM, mean time for hCG to return to normal, use of chemotherapy, and presence of distant disease was greater in HeCM. These findings suggest that HeCM may behave in a more aggressive fashion, although analysis of more patients is needed.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 161, Tuesday Afternoon