Mutational analysis of selected high-grade malignancies in a premenopausal gynecologic cancer population: a potential for targeted therapies?

Background: In 2017, there will be 107,000 cases of gynecologic cancer diagnosed in the US with an overall survival of around 70%-most occurring in post-menopausal individuals. In this study, we have examined a younger (≤ 40 years of age) subpopulation of these women with high grade/ high stage gynecologic malignancies, attempting to identify unique genetic abnormalities or combinations thereof through tissue block specimens. This information was then analyzed in light of known target therapies to see if genetic analysis in this setting would yield significant therapeutic advantage. Methods: We retrospectively evaluated patients with high grade/high stage gynecologic cancers (≤ 40 years of age), examined the presence and status of 400 oncogenes and tumors suppressor genes from Formalin-fixed, Paraffin-embedded (FFPE) tissue and functionally classified mutations by SIFT and Polyphen. Results: Twenty women were identified and stratified into positive and negative outcomes. No demographic, clinicopathologic or treatment factors were significant between these groups. Of the 400 genes evaluated, twelve mutations were significant between the groups, six with targeted therapies. Mutations associated with negative outcomes within histologies/locations were evaluated: ERBB3 in epithelial (ovarian), ALK/GPR124/KMT2D in neuroendocrine (ovarian/endometrial), ROS1/EGFR, ROS1/ERBB3/KMT2D/NIRK1 and GPR124 in sarcoma. All negative outcomes were void of mutations in APC/ABL2. A predictive model for negative outcomes in our cohort was developed from these data: AKAP9-/MBD1-/APC-/ABL2- with a mutation load of > 20.5. Conclusions: Unique multi-gene and mutational outcome correlations were identified in our cohort. Resulting complex mutational profiles in distinctly aggressive gynecologic cancers suggested potential for novel therapeutic treatment. Future larger scale studies will be needed to correlate the genotypic and phenotypic features identified here (AU)

Potential opportunities to reduce cervical cancer by addressing risk factors other than HPV / 부인종양

Cervical cancer is the most common cancer in developing world and 80% of global burden is reported from these nations. Human papillomavirus along with poverty, illiteracy/lower education level and standards, multi-parity, tobacco, malnutrition and poor genital hygiene may act synergistically to cause cervical cancer. Risk factor of cervical cancer may in itself be the reason for non-viability of cervical cancer vaccine program in this part of the world. Interventions to address these risk factors in addition to vaccination of girls before their sexual debut may hold promises of reducing the morbidity and mortality of female genital cancers.

Proteomics in obstetrics and gynecology.

Proteomics helps to understand the basic biological processes critical to normal cellular functions as well as the development of diseases. It identifies the essential components of these processes and exploits these components as targets in the development of new methods to prevent or treat diseases. Proteomics, although in an infancy stage in India, has the potential to complement and further enlarge the wealth of information in medicine, especially in the field of cancer. This article reviews the recent progress in proteomic techniques and their applications in the field of obstetrics and gynecology.

Laparoscopic pelvic and para-aortic lymphadenectomy / 한양의대학술지

Laparoscopic surgery has many benefits over a conventional abdominal approach. These include less blood loss, low morbidity, shorter recovery time, shorter hospital stay, and shorter time interval to adjuvant therapy. With advances of laparoscopic instruments and surgical skills, laparoscopic surgery is becoming a dominant paradigm in the surgical management of gynecologic cancers. Advanced laparoscopic procedures including radical hysterectomy and trachelectomy with pelvic and para-aortic lymphadenectomy are now used in the management of early cervical cancer. For patients with apparent early-stage endometrial and ovarian cancer, laparoscopic complete staging operation including pelvic and para-aortic lymphadenectomy can be applied. Of several laparoscopic surgical procedures, laparoscopic pelvic and para-aortic lymphadenectomy is a cornerstone in the management of gynecological cancers cancers. The evaluation of lymph node status has an important role in diagnosis, treatment, and prognosis of gynecologic cancers because lymphatics are the main pathways of dissemination of gynecologic cancers. Laparoscopic pelvic and para-aortic lymphadenectomy is feasible and safe without increase of perioperative complications and decrease in patient's survival in gynecologic cancers, if it is performed by an experienced laparoscopic oncologic surgeon. During the last 10 years, laparoscopic procedures including pelvic and para-aortic lymphadenectomy in over 600 patients with gynecologic cancers were underwent in our department. We have found that the surgical and oncologic outcomes were similar or even better compared to conventional laparotomic procedures. In conclusion, the gynecologic oncologist should be familiar with lymphatic anatomy and laparoscopic skills to perform pelvic and para-aortic lymphadenectomy, because laparoscopic management of gynecologic cancers will be the choice of surgical treatment in the near future.