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Objective: The cyclin-dependent kinase inhibitor p27 has been shown to mediate cell growth arrest in response to various environmental stimuli. p27 protein levels have shown prognostic value in several different types of cancer. We examined the prognostic value of p27 protein expression in endometrial cancer, the most common gynecologic malignancy., Methods: A total of 95 paraffin-embedded tumor blocks were obtained and stained via immunohistochemical techniques with a monoclonal antibody against p27. Ten high-power fields were evaluated per slide with at least 1000 cells per slide and two slides per specimen evaluated by two reviewers for nuclear and cytoplasmic staining. The specimens were evaluated for associations with age, stage, grade, and histology. Statistical analysis was performed using the Student t test, chi(2) Kaplan-Meier, and likelihood ratios to assess the data and to generate P values., Results: A total of 91 patients met inclusion criteria for statistical analysis. Fifty-three patients were stage I, 13 stage II, 14 stage III and 11 stage IV with a positive stain (>50% of cells) for p27 obtained in 32.1, 23.1, 35.7, and 36.4%, respectively (Student t test P = 0.77). Survival data were available on 24 advanced stage patients. p27 protein immunostaining showed no association with patient survival. We also found no association of p27 staining with age or histology. Notably, we found a trend in increasing staining with increase in grade, particularly with stage I patients. Also, there was an association of the nuclear and cytoplasmic staining and stage (P = 0.05), but it had no correlation with patient survival., Conclusion: Our study showed decreased p27 protein staining in endometrial cancers compared to normal endometrial cells. We found that p27 protein staining shows no association with stage, age, or histology and is not prognostic for survival in advanced endometrial cancers. However, there may be a trend associated with increased p27 protein staining with advanced grades of tumors., (Copyright 2001 Academic Press.)

Objective: The purpose of this paper was to evaluate the age-specific survival for women diagnosed with endometrioid adenocarcinoma of the uterus., Methods: A retrospective analysis was conducted of 328 patients diagnosed with endometrioid adenocarcinoma of the uterus between January 1990 and December 1997. Patients were followed for 3 to 96 months with a mean of 43 months. The impact of age on survival was assessed using Cox proportional hazard regression and multivariate analysis for age, stage, and grade. Stage and grade were analyzed using log-rank tests, and survival curves were generated by the Kaplan-Meier method., Results: A total of 328 patients were evaluated. Multivariate analysis revealed age, stage, and grade were all significant independent predictors of survival (P < 0.0001). Age-specific survival varied from a high of 90% at age 40 to a low of 55% at age 80. Interval age-specific survival decreased below 86% at age 50. Subset analysis of patients younger than 50 compared with older patients revealed no difference in surgical stage or grade of tumors among these patients. Patients older than 50, however, were 41% more likely to receive adjuvant radiation therapy., Conclusion: Age is a specific, significant predictor of outcome in endometrioid adenocarcinoma of the uterus. Survival decreases significantly in patients older than 50. This decreased survival associated with age is unrelated to surgical stage or grade of adenocarcinoma. Decreased survival could involve molecular differences in the developing endometrial cancer or an increased risk of death from other non-cancer-related factors., (Copyright 2000 Academic Press.)

Objective: The aim of this study was to investigate the relationship between the expression of the TGF-beta ligands and TGF-beta receptors to the expression of p27(Kip1), a TGF-beta-regulated gene, in endocervical cancer., Methods: To examine the expression of TGF-beta and p27(Kip1) in malignant transformation of the uterine endocervix, a panel of 23 formalin-fixed and paraffin-embedded human cervical specimens, including 8 with benign endocervical glands, 8 with cervical adenocarcinoma in situ, and 7 with cervical adenocarcinomas, was used. Tissues were immunostained with polyclonal antibodies that react specifically with TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF-beta RII, and p27(Kip1)., Results: Immunostaining for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF-beta RII, and p27(Kip1) was detected in normal endocervix, with the TGF-betas showing weak cytoplasmic staining, while p27(Kip1) showed strong nuclear staining. Expression of TGF-beta increased significantly upon neoplastic transformation with the TGF-beta ligands and receptors showing strong cytoplasmic staining in adenocarcinoma in situ compared to normal endocervix. Interestingly, expression of TGF-beta was lower in adenocarcinoma than in adenocarcinoma in situ, but still significantly higher than in normal endocervix. TGF-beta 2 and TGF-beta 3 showed higher levels of immunostaining than TGF-beta 1 in adenocarcinomas. In contrast, p27(Kip1) protein expression decreased with progressive malignancy, with lower p27(Kip1) protein levels detected in adenocarcinoma than in adenocarcinoma in situ, while normal endocervix showed the highest level of p27(Kip1) protein expression., Conclusion: Elevated expression of the TGF-beta ligands and receptors is found in both cervical adenocarcinoma in situ and adenocarcinoma compared to normal endocervix. In contrast, a progressive decrease in p27(Kip1) occurs upon neoplastic transformation of the normal endocervix to cervical adenocarcinoma. These results suggest that neoplastic transformation of the endocervix may be related to dysregulation of TGF-beta and p27(Kip1) seen as an elevation of TGF-beta and a reduction of p27(Kip1) expression that may lead to loss of cell cycle control.

Background: Primary peritoneal carcinoma is an uncommon disease, characterized by peritoneal carcinomatosis without other identifiable primary tumor. It typically presents resembling ovarian cancer, with abdominal pain and distention and in an advanced stage. We report a unique presentation of this disease., Case: A 76-year-old woman had severe glandular dysplasia on a screening Papanicolaou smear. An ectocervical lesion was biopsied, revealing moderately differentiated adenocarcinoma. Cervical stenosis prevented sampling of the endocervix and endometrium. Colonoscopy and mammography did not reveal malignancy. Total abdominal hysterectomy with bilateral salpingo-oophrectomy was performed. Surgery revealed surface implants on the pelvic organs, with minimal involvement of the ovaries. Histologic examination revealed adenocarcinoma with papillary serous differentiation. Surgical and microscopic findings were consistent with a diagnosis of primary peritoneal carcinoma., Conclusion: Primary peritoneal carcinoma usually presents in a manner similar to that of ovarian cancer, but atypical presentations also occur. While a Papanicolaou smear suggestive of carcinoma usually represents a primary cervical malignancy, this case serves as a reminder that other metastatic malignancies should be considered., (Copyright 2000 Academic Press.)

Bartholin's gland carcinomas are a rare entity. A case of a recurrent Bartholin's gland carcinoma is described. These neoplasms have a myriad of treatment options for primary therapy but there is a paucity of information regarding treatment for a lethal recurrence. The patient's primary therapy consisted of an initial wide local excision followed by radiation therapy with chemosensitization. She was disease-free for 2 years before her recurrence. A novel treatment approach incorporating a mulitdisciplinary en bloc radical surgery is described. The patient is alive and well without evidence of disease at 22 months.

Background: The original description of the Cherney incision includes bilateral ligation of the inferior epigastric vessels to increase incision width [1]. However, in patients with compromised abdominal wall vasculature, ligation may lead to healing complications., Case: Our patient experienced necrosis of the right rectus muscle after undergoing pelvic surgery via a Cherney incision. During the procedure, attempts were made to retain both inferior epigastric arteries, but the right was transected and ligated. Sepsis developed and myofascitis was diagnosed. The interesting radiographic findings of myofascitis are also presented., Conclusion: The vasculature of our patient's abdominal wall may have been compromised after four previous transverse abdominal incisions, and the ligation of the right inferior epigastric vessel may have contributed to postoperative complications., (Copyright 1998 Academic Press.)

Ror1 is an orphan cell surface receptor with strong homology to the tyrosine kinase domain of growth factor receptors, in particular the Trk family. Southern blot analysis of genomic DNA from somatic cell hybrids revealed that Ror1 is located on chromosome 1. We have mapped the Ror1 gene to chromosome 1p12-p32 using PCR on a somatic cell hybrid panel that subdivides chromosome 1p. We have further localized the gene to chromosome 1p31-p32 by fluorescence in situ hybridization using a PAC clone that contains the Ror1 gene.

By screening a human fetal brain cDNA expression library using a monoclonal anti-phosphotyrosine antibody, we have isolated a cDNA clone encoding a receptor type protein-tyrosine kinase belonging to the EPH family, NET (neuronally expressed EPH-related tyrosine kinase). NET shows 87% homology in nucleotide sequence and 99% homology in the deduced amino acid sequence to rat elk, suggesting that NET is the human homologue of elk. The NET gene is mapped to human chromosome 3q21-q23 by PCR screening of a human-rodent somatic cell hybrid panel and by fluorescence in situ hybridization. Examination of NET mRNA expression in several human tissues has shown that the NET gene is expressed preferentially in brain as a 5-kb transcript. Steady-state levels of NET mRNA in human brain are greater in the midterm fetus than in the adult. Lower levels of NET mRNA are found in fetal kidney and adult skeletal muscle. The expression pattern of NET mRNA thus differs from that of elk, suggesting that these two gene products may perform distinct roles in human and rat. NET transcripts are detected in human NTera-2 teratocarcinoma cells after retinoic acid-induced neuronal differentiation. Several human tumor cell lines derived from neuroectoderm including primitive neuroectodermal tumor, small cell lung carcinoma, and neuroblastoma also express NET transcripts. Since the NET mRNA expression in human brain is developmentally regulated and is induced during neuronal differentiation, NET potentially plays important roles in human neurogenesis.

There is increasing evidence that neutrophins and their receptors play an important role in regulating development of both the central and the peripheral nervous systems. Human TRK-A (NTRK1) and TRK-C (NTRK3) have been cloned and sequenced, but only a truncated form of human TRK-B has been published. Therefore, we isolated complementary DNAs spanning the entire coding region of both human full-length and truncated forms of TRK-B from human brain cDNA libraries. Human full-length TRK-B codes for a protein of 822 amino acid residues. The putative mature peptide sequence is 49% homologous to human TRK-A and 55% to full-length human TRK-C, with 40% amino acid identify among TRK-A, -B, and -C. Nine of 13 cysteine residues, 4 of 12N-glycosylation sites in the extracellular domain, and 10 of 13 tyrosine residues in the intracellular domain are conserved among human TRK-A, -B, and -C. There is a cluster of 10 serine residues in the juxtamembrane region of TRK-B that is absent in TRK-A. Two major sizes of TRK-B transcripts were expressed in human brain. Northern blot analysis using probes specific for the extracellular or the tyrosine kinase domain revealed that the 9.5-kb band encodes the full-length TRK-B mRNA and the 8.0-kb band encodes the truncated form of TRK-B mRNA. By fluorescence in situ hybridization and somatic cell hybrid mapping, the human TRK-B gene was localized to chromosome 9q22.1.

A characteristic translocation t(2;13)(q35;q14) has been previously identified in the pediatric soft tissue tumor alveolar rhabdomyosarcoma. We have assembled a panel of lymphoblast, fibroblast, and somatic cell hybrid cell lines with deletions and unbalanced translocations involving chromosome 2 to develop a physical map of the distal 2q region. Twenty-two probes were localized on this physical map by Southern blot analysis of the mapping panel. The position of these probes with respect to the t(2;13) rhabdomyosarcoma breakpoint was then determined by quantitative Southern blot analysis of an alveolar rhabdomyosarcoma cell line with two copies of the derivative chromosome 13 and one copy of the derivative chromosome 2 and by analysis of somatic cell hybrid clones derived from an alveolar rhabdomyosarcoma cell line. We demonstrate that the t(2;13) breakpoint is situated within a map interval delimited by the distal deletion breakpoint in fibroblast line GM09892 and the t(X;2) breakpoint in somatic cell hybrid GM11022. Furthermore, from a comparison of our data with the linkage map of the syntenic region on mouse chromosome 1, we conclude that the t(2;13) breakpoint is most closely flanked by loci INHA and ALPI within this map interval.