The following articles appeared in this month's issues of the surveyed journals. Articles that seem to be of most interest to the practicing gynecologic oncologist are included. The journals that are surveyed are New England Journal of Medicine, Journal of Clinical Oncology, Gynecologic Oncology, Cancer, American Journal of Obstetrics and Gynecology, Lancet, Cancer Research, Obstetrics and Gynecology, Journal of the National Cancer Institute, Journal of the American Medical Association. The participants in this program are the active clinical fellows at Memorial Hospital: Bhavana Pothuri, Mario Leitao, Christopher Awtrey, Sarah Ferguson, Alan Schlaerth and Rami Eitan. The managing editor is Douglas Levine. Comments, questions, complaints and suggestions are always welcome, please E-mail us at: VJC@smgo.org or click here.  To subscribe or unsubscribe to the VJC, click here.

Gynecologic Oncology – Mario Leitao

Title: p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer

Authors: Tsuyoshi Okuda, Junko Otsuka, Akihiko Sekizawa, Hiroshi Saito, Reiko Makino, Miki Kushima, Antonio Farina, Yuzuru Kuwano and Takashi Okai.

Source: Gynecologic Oncology, Volume 88, Issue 3, March 2003, Pages 318-325.

Summary: Tissue from 64 retrospectively identified Japanese patients with clear cell and endometrioid ovarian carcinoma was analyzed for K-ras mutation, p53 overexpression and mutation.  K-ras was not associated with outcome. No evidence of p53 mutation was detected in clear cell patients, but p53 mutation was detected in 63.0% of endometrioid patients.  Only p53 alteration and endometriosis were associated with outcome in the endometrioid tumors after multivariate analysis.

Click here for abstract from GYN Oncology

Title: Radical vaginal trachelectomy and pelvic lymphadenectomy for preservation of fertility in early cervical carcinoma

Authors: Alexander F. Burnett, Lynda D. Roman, Anne T. O'Meara and C. Paul Morrow.

Source: Gynecologic Oncology, Volume 88, Issue 3, March 2003, Pages 419-423.

Summary: Second U.S. report on the experience with radical vaginal trachelectomy. The authors report on 21 patients with squamous and adenocarcinoma.  There have been no recurrences in 31 months of follow-up and three of 18 patients were able to become pregnant. Radical trachelectomy remains a viable fertility sparing option for highly selected and motivated patients.

Click here for abstract from GYN Oncology

Journal of Clinical Oncology - Bhavana Pothuri

Title: Human Kallikrein 6 (hK6): A New Potential Serum Biomarker for Diagnosis and Prognosis of Ovarian Carcinoma

Authors: Diamandis, Eleftherios P., Scorilas, Andreas, Fracchioli, Stefano, van Gramberen, Marleen, de Bruijn, Henk, Henrik, Alfthan, Soosaipillai, Antoninus, Grass, Linda, Yousef, George M., Stenman, Ulf-Hakan, Massobrio, Marco, van der Zee, Ate GJ, Vergote, Ignace, Katsaros, Dionyssios

Source: J Clin Oncol 2003 21: 1035-1043

Summary: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma.  Serum hK6 concentration between normal and benign disease patients was not different. However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 µg/L; P < .001).  Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses.  Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis. 

Click here for abstract from JCO

In this same issue there is a nice review article on granulosa cell tumors by Susan Tinsley Schumer and Stephen A. Cannistra.  See JCO 2003 21: 1180-1189

Journal of the National Cancer Institute – Rami Eitan

The following article is important when counseling patients at high risk for breast or ovarian cancer.  The important take-home message is that, unlike ovarian cancer, a large portion of hereditary breast cancer is not BRCA-related.

Title: Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations

Authors: Gillian S. Dite, Mark A. Jenkins, Melissa C. Southey, Jane S. Hocking, Graham G. Giles, Margaret R. E. McCredie, Deon J. Venter, and John L. Hopper

Source: J Natl Cancer Inst 2003; 95: 448-457.

Summary: 1567 unselected case patients diagnosed with breast cancer before age 60 years were recruited to a population-based, case–control-family study.  Extensive BRCA1 and BRCA2 mutation testing was carried out for 788 case patients diagnosed before age 40 years.  Cumulative risks of breast cancer to age 50 years in the sisters, mothers, and aunts of the case patients, respectively, were 6, 3, and 2 times the population risk if the case patient was younger than age 40 years at diagnosis.  Less than one-third of the excess of breast cancers in relatives of case patients diagnosed before age 40 years that are attributed to familial factors are BRCA1- or BRCA2-related.  Mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer, especially in young women.

Click here for abstract from JNCI

The following article sheds a unique light on the etiology of borderline tumors and suggests that they develop from a completely separate pathobiologic pathway than invasive ovarian carcinomas. 

Title: Mutations in BRAF and KRAS Characterize the Development of Low-Grade Ovarian Serous Carcinoma

Authors: Gad Singer, Robert Oldt, III, Yoram Cohen, Brant G. Wang, David Sidransky, Robert J. Kurman, and Ie-Ming Shih

Source: J Natl Cancer Inst 2003; 95: 484-486.

Summary: To determine the role of mutations in BRAF and KRAS in ovarian carcinoma, we analyzed both genes for three common mutations. Mutations in either codon 599 of BRAF or codons 12 and 13 of KRAS occurred in 15 of 22 (68%) invasive micropapillary serous carcinomas and in 31 of 51 (61%) serous borderline. None of the tumors contained a mutation in both BRAF and KRAS. In contrast, none of the 72 aggressive high-grade serous carcinomas analyzed contained any of the studied mutations. The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways.

Click here for abstract from JNCI

Obstetrics and Gynecology – Alan Schlaerth

Title: Endometrial cancer: the potential role of cervical cytology in current surgical staging

Authors: Brent DuBeshter, Colleen Deuel, Shaun Gillis, Christopher Glantz, Cynthia Angel and David Guzick

Source: Obstetrics & Gynecology, Volume 101, Issue 3, March 2003, Pages 445-450.

Summary: This study evaluated the cervical cytology, the tumor grade from endometrial sampling, and myometrial invasion in 300 patients to assess their risk of nodal metastasis in endometrial carcinoma. The presence of endometrial cells on cervical cytology, deep myometrial invasion, and high-grade tumor were associated with 91%, 87%, and 83% of the cases of nodal spread, respectively. The risk of lymph node spread in patients with normal cervical cytology was 2%. The authors recommend lymphadenectomy in all patients with endometrial cancer until a reliable system is found to identify those with negligible (less than 1%) risk of nodal spread.

Click here for abstract from Obstetrics & Gynecology

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American Journal of Obstetrics and Gynecology – Chris Awtrey

Title: Comparison of cell collection and direct visualization cervical cancer screening adjuncts.

Authors: Parham GP

Source:  Am J Obstet Gynecol 2003 Mar;188(3):S13-20.

Summary: This is a collection of articles about the new developments in cervical cancer screening with an introduction by Dr. DiSaia. The first, Dr. Berek's article, is an exploration of the guidelines of Bethesda III and the reasons for the changes made, all of which appear to greatly simplify the classification system. The second article, by Dr. Felix investigates the shedding of dysplastic cells from the cervix allowing for a positive pap test and factors associated with a falsely negative one. The third article, by Dr. Parnam looks at a new approach to cervical examination, the PapSure screening exam. This cervical screening examination combines the traditional Pap smear with direct visual screening test, speculoscopy. The new test detected 33% more HGSIL and 4 times as many LGSIL than conventional Pap smear alone.

Click here for abstract from Am J Ob Gyn

New England Journal of Medicine – Bhavana Pothuri

Nothing of interest this month

Journal of the American Medical Association – Rami Eitan

Cancer – Sarah Ferguson

Title: Histopathologic Score Predicts Recurrence Free Survival after Radical Surgery in Patients with Stage IA2-IB1-2 Cervical Carcinoma.

Authors: Grisaru DA, Covens A, Franssen E, Chapman W, Shaw P, Colgan T, Murphy J, DePetrillo D, Lickrish G, Laframboise S, Rosen B.

Source: Cancer 2003 Apr 15;97(8):1904-8.

Summary: Eight hundred and seventy one women with FIGO stage IA2-1B2 cervical carcinoma were reviewed. There were 66 recurrences with a median follow-up of 49 months. Maximum depth of invasion(>10mm), positive pelvic lymph nodes and presence of CLS were combined as the best predictors for survival. Those women with all 3 factors present had a 5-year recurrence free survival of 65%. These women would be most suitable for adjuvant postoperative therapy.

Click here for abstract from Cancer

Lancet – Chris Awtrey

Nothing of interest this month

Cancer Research – Sarah Ferguson

Nothing of interest this month