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 and American Journal of Surgical Pathology. The participants in this program are the active clinical fellows at Memorial Hospital: Mario Leitao, Christopher Awtrey, Sarah Ferguson, Alan Schlaerth, Destin Black and Margrit Juretzka. 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 – Christopher Awtrey

[Ed note: This is one of two articles in this month's issue of GYN Oncology reporting on the role of c-KIT in uterine sarcomas.  The other article can be found on pages 3-8.]

Title: Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT

Authors: R.S. Rushing, S. Shajahan, D. Chendil, J. Wilder, J. Pulliam, E. Lee, F Ueland, J van Nagell, M. Ahmed, S. Lele

Source: Gynecologic Oncology, Volume 91, Issue 1, October 2003, Pages 9-14.

Summary: The success of targeted biologic agents such as the tyrosine kinase inhibitor STI571 has sparked interest in the use of these agents in treating other types of malignancies. Uterine malignancies are relatively rare, but carry a high risk of recurrence and mortality rate. Because of the embryologic and histologic similarities between GIST and uterine sarcomas interest of the use of this form of targeted therapy is high. In this study 25 uterine sarcomas including 14 MMMT, 7 LMS,  2 ESS and 2 high grade heterologous sarcomas were analyzed for expression of c-KIT by IHC. A mutational analysis was then performed on all the tumors for the KIT-activating mutation. Two mutation sites in exon 11 or 17 are associated with response of GIST to STI571. The group found that all 25 tumors expressed c-kit by IHC and that this staining was moderate to strong in 22 of the 25 cases. In only one tumor was there a deletion of both exons 11 and 17; the rest harbored no mutation. The authors conclude that despite the fact that the tumors have IHC evidence of c-KIT, STI571 is unlikely to work in these tumors as they lack the KIT-activating mutation.

Click here for abstract from Gynecologic Oncology

Return to top of page

Journal of Clinical Oncology - Mario Leitao

Title: Prognostic Significance of p53 Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

Authors: Havrilesky, Laura, Darcy, Kathleen M., Hamdan, Hasnah, Priore, Roger L., Leon, Jorge, Bell, Jeffrey, Berchuck, Andrew

Source: J Clin Oncol 2003 21: 3814-3825

Summary: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a GOG randomized phase III treatment protocol. Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P = .014) and a 60% reduction in risk of disease progression (P = .014) for women with such mutations. However, these striking risk reductions increased over time (P < .02) and eventually disappeared with longer follow-up. Overexpression of p53 was associated with tumor grade but not with patient outcome. Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit.

Click here for abstract from JCO

Return to top of page

Journal of the National Cancer Institute – Alan Schlaerth

Nothing of interest this month

Obstetrics and Gynecology – Margrit Juretzka

Title: Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer

Authors: Walter H. Gotlieb, Mario E. Beiner, Bruria Shalmon, Yaacov Korach, Yaacov Segal, Nissim Zmira, Joure Koupolovic and Gilad Ben-Baruch

Source: Obstetrics & Gynecology, Volume 102, Issue 4, October 2003, Pages 718-725

Summary: The authors report on 13 patients with endometrial adenocarcinoma who underwent conservative treatment with progestins. Mean age of patients at diagnosis was 31 years. Eleven patients had well-differentiated adenocarcinomas; the other 2 had moderately differentiated tumors. All patients had a response with a mean time of 3.5 months. Three patients delivered 9 viable infants (2 patients pregnant at publication). While 6 patients had a recurrence (median 40 months), four were treated with further progestin therapy (2/4 subsequently had surgical treatment revealing adenocarcinoma on final pathology). All patients remained without evidence of disease with a mean follow-up time of 82 months. The authors conclude that conservative management of well-differentiated endometrial carcinoma in young patients does not seem to worsen the prognosis.

Click here for abstract from Obstetrics & Gynecology

Title: Changes in cervical cancer incidence after three decades of screening US women less than 30 years old

Authors: Pamela G. Chan, Hai-Yen Sung and George F. Sawaya

Source: Obstetrics & Gynecology, Volume 102, Issue 4, October 2003, Pages 765-773

Summary: The authors report on the incidence trends of invasive cervical cancer in US women under 30 years of age based on data from  the SEER database. Between 1973 to 1999, the incidence rates of cervical carcinoma declined overall (estimated annual changes of -0.94% (95% CI -1.47%, -0.41%). While incidence rates of squamous cell carcinoma declined with an estimated annual change of -1.10% (95% CI -1.59%, -0.62%), rates of adenocarcinoma increased (+2.90%; 95% CI 1.34%, 4.49%). The authors conclude that because of the small number of actual cases, caution must be exercised in interpreting these trends.

Click here for abstract from Obstetrics & Gynecology

American Journal of Obstetrics and Gynecology – Sarah Ferguson

Title: Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades

Authors: Jill S. Barnholtz-Sloan, Ann G. Schwartz, Faisal Qureshi, Suzanne Jacques, John Malone and Adnan R. Munkarah

Source: American Journal of Obstetrics and Gynecology, Volume 189, Issue 4, October 2003, Pages 1120-1127

Summary: This population-based study uses the SEER data base to compare changes in demographics, prognostic factors and relative survival in women with invasive epithelial ovarian cancer (EOC) between three decades.  There was a significant increase in the proportion of African American women diagnosed with invasive EOC. There was an increase in the proportion of all women undergoing primary surgery and women with advanced disease undergoing primary surgery over the three decades.  Overall relative survival increased over the past three decades. Two year relative survival significantly increased for Caucasian women, however there was no change in 5-year survival. There was no significant change in 2 or 5 year survival over the three decades for African American women and they continued to have a worse prognosis compared to Caucasian women. The authors conclude the increase in minorities with a diagnosis of EOC reflects increased access to health care or a changing population base. The increase in women undergoing primary surgery reflects the changing practice patterns, recognizing the importance of primary debulking surgery in the treatment of women with EOC. In addition, the improved survival likely is due to the combination of surgery, introduction of platinum chemotherapy and general supportive care.

Click here for abstract from Am J Ob/Gyn

New England Journal of Medicine – Mario Leitao

Journal of the American Medical Association – Margrit Juretzka

Cancer – Destin Black

Authors: Rouba Ali-Fehmi, M. D., Mingxin Che, M.D., Ibrahim Khalifeh, M.D., John M. Malone, M.D., Robert Morris, M.D., W. Dwayne Lawrence, M.D., Adnan R. Munkarah, M.D.

Source: Cancer, October 1, 2003, Vol.98, Number 7; Pages 1423 - 1429

Lancet – Sarah Ferguson

Nothing of interest this month

Cancer Research – Destin Black

Nothing of interest this month