Abnormal villous morphology associated with triple trisomy of paternal origin.

The vast majority of trisomies in spontaneous abortions (SAB) are single and of maternal origin, most frequently due to meiosis I errors. Triple trisomies are exceedingly rare (approximately 0.05% of spontaneous abortions), most often of maternal origin, and associated with increased maternal age. Some trisomic SAB specimens can exhibit abnormal villous morphology simulating a partial hydatidiform mole, a distinct form of hydatidiform mole characterized by diandric triploidy. A SAB specimen from a 27-year-old woman, G1P0 at 8 weeks gestational age, was reviewed in consultation to address the finding of morphological features suggestive of a partial hydatidiform mole but DNA ploidy analysis yielding a diploid result. The villi were irregularly shaped and hydropic but lacked trophoblastic hyperplasia; p57 expression was retained. Since fully developed features of a partial hydatidiform mole were lacking, additional analysis was performed. Molecular genotyping and single nucleotide polymorphism array analysis demonstrated biparental diploidy with trisomy of chromosomes 7, 13, and 20, all of paternal origin. The three trisomies may have originated from paternal meiosis II errors, or from mitotic nondisjunction. We believe this to be the first report of triple trisomy in a SAB confirmed to be of paternal origin.

Histologic alterations from neoadjuvant chemotherapy in high-grade extremity soft tissue sarcoma: clinicopathological correlation.

Histologic response to chemotherapy is generally regarded as an independent prognostic variable in bone sarcomas, both osteosarcoma and Ewing's sarcoma. In soft tissue sarcomas, however, descriptions of histologic alterations from chemotherapy and correlative outcome studies are much more limited. Herein we report clinicopathological findings from a homogeneously treated group of 31 patients with tumor stage T2 grade 3 extremity soft tissue sarcomas treated with the same neoadjuvant chemotherapy followed by surgical excision, treated by the same medical oncologist and orthopedic surgeon. Histologic response to therapy was evaluated by multiple parameters using a semiquantitative grading system. Based upon the percentage of post-treatment viable tumor, tumors were arbitrarily categorized similarly to Huvos score as showing excellent (< or =5% viability), moderate (6%-49% viability), or poor (> or =50% viability) responses. Nineteen percent had excellent, 10% had moderate, and 71% had poor responses. These histologic response groups did not correlate with overall or event-free survival. For example, of the 22 patients showing a "poor" response, 13 were cured. Similarly, other histologic parameters, including percentages of necrosis, fibrosis/hyalinization, and cellular degeneration, did not correlate with outcome. Chemotherapy induces profound tissue alterations in soft tissue sarcomas. However, histologic alteration by itself may not be a reliable prognostic variable. Correlation of all data from clinical, imaging, and pathological observations by a multidisciplinary tumor board should have greater prognostic value than histology alone. Finally, although the histologic grading system used in this study could not be validated, the criteria we employed are simple and reproducible and take into account the major histologic patterns seen after therapy, and would be amenable for use in future studies.

Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.

PURPOSE: Ovarian and uterine carcinomas manifest several differentiation patterns resembling those seen in nonneoplastic epithelia of the gynecologic tract. Specific oncogene and tumor suppressor gene defects have been associated with particular differentiation patterns in carcinomas arising in either the uterus or ovary. For instance, ovarian and uterine carcinomas with endometrioid differentiation frequently show beta-catenin mutations. Whereas type of differentiation is considered in the treatment of uterine carcinomas, it does not presently contribute to decisions about treatment of ovarian carcinomas. A widely accepted view is that the accumulation of specific gene defects and gene expression changes underlies phenotypic traits of cancers, including their response to treatment. EXPERIMENTAL DESIGN: Using oligonucleotide microarrays to assess gene expression in 103 primary ovarian and uterine carcinomas, we sought to address whether organ of origin or type of differentiation (histotype; endometrioid versus serous) had a more substantial effect on gene expression patterns. RESULTS: We found that effects on gene expression due to organ of origin and histotype are similar in magnitude and are parallel in that organ effects are similar in the two histotypes and histotype effects are similar in the two organs. In addition, ovarian and uterine endometrioid adenocarcinomas with beta-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects. CONCLUSIONS: Our results illustrate how organ of origin, type of differentiation, and specific molecular defects all contribute to gene expression in the most common types of ovarian and uterine cancers. The findings also imply gene expression data will be of value for stratifying ovarian cancer patients for new treatment approaches.