Borderline ovarian tumors account for 15% of epithelial ovarian cancers and are different from invasive malignant carcinoma. Majority are early stage, occurring in women in the reproductive age group, where fertility is important. We reviewed retrospectively 247 such cases treated at the Gynaecological-Oncology Unit, KK Women's and Children's Hospital, between January 1991 and December 2004. The mean age was 38 years (16-89 years). Majority of the cases (92%) were FIGO stage I (Ia, 75%; Ib, 1%; and Ic, 16%). Seven (3.5%) patients were diagnosed as having stage II disease, six (2.5%) as stage IIIa, two (1%) as stage IIIb, and four (2%) as stage IIIc. Histological origin was as follows: mucinous (68%), serous (26%), endometrioid (2.6%), and clear cell (1.2%). Primary surgical procedures undertaken were as follows: hysterectomy with bilateral salpingo-oophorectomy (52%), unilateral salpingo-oophorectomy (33%), or ovarian cystectomy (15%). Adjuvant chemotherapy was administered in 13 patients (5.2% of cases), of which 4 patients were given chemotherapy only because of synchronous malignancies. There were six recurrences (2.4% of cases). Overall mean time to recurrence was 59 months. Recurrence rate for patients who underwent a primary pelvic clearance was 1.6% compared to fertility-sparing conservative surgery (3.3%; although P= 0.683). No significant difference was noted in recurrence and mortality between staged versus unstaged procedures. The overall survival rate was 98.0%. There were a total of five deaths (2.8%): three (1.5%) from invasive ovarian/peritoneal carcinoma and two from synchronous uterine malignancies. It appears that surgical resection is the mainstay of treatment, with conservative surgery where fertility is desired or pelvic clearance if the family is complete. Surgical staging is important to identify invasive extraovarian implants that portend an adverse prognosis. The role of adjuvant chemotherapy is not established.
AimTo determine the frequency of MED12 mutations in a series of 112 breast phyllodes tumours, and to correlate the findings with clinicopathological parameters and survival outcomes. Methods Phyllodes tumours from the Department of Pathology, Singapore General Hospital, were classified into benign, borderline and malignant categories. Genomic DNA from formalin-fixed paraffin-embedded phyllodes tumours was extracted, purified and subjected to ultra-deep-targeted amplicon sequencing across exon 2 of the MED12 gene. Sequencing was performed on the Illumina MiSeq next-generation sequencing platform and bioinformatics analysis applied. Appropriate statistical analyses were carried out. Results There were 66 benign, 32 borderline and 14 malignant tumours, with 43 (65.1%), 21 (65.6%) and 6 (42.8%) disclosing MED12 mutations (missense, splice site, indel), respectively. For 97 cases with available follow-up, there were 10 (10.3%) recurrences. Patients with phyllodes tumours that harboured MED12 mutations experienced improved disease-free survivals, with higher recurrence likelihood in those without MED12 mutations (HR 9.99, 95% CIs 1.55 to 64.42, p=0.015). Conclusions Similar to fibroadenomas, phyllodes tumours show a high frequency of MED12 mutations, affirming the close biological relationship between these fibroepithelial neoplasms.
Mucinous epithelial ovarian cancer has a poor prognosis in the advanced stages and responds poorly to conventional chemotherapy. We aim to elucidate the clinicopathological factors and incidence of HER2 expression of this cancer in a large Asian retrospective cohort from Singapore. Of a total of 133 cases, the median age at diagnosis was 48.3 years (range, 15.8–89.0 years), comparatively younger than western cohorts. Most were Chinese (71%), followed by Malays (16%), others (9.0%), and Indians (5%). 24% were noted to have a significant family history of malignancy of which breast and gastrointestinal cancers the most prominent. Majority of the patients (80%) had stage I disease at diagnosis. Information on HER2 status was available in 113 cases (85%). Of these, 31 cases (27.4%) were HER2+, higher than 18.8% reported in western population. HER2 positivity appeared to be lower among Chinese and higher among Malays patients (p = 0.052). With the current standard of care, there was no discernible impact of HER2 status on overall survival. (HR = 1.79; 95% CI, 0.66–4.85; p = 0.249). On the other hand, positive family history of cancer, presence of lymphovascular invasion, and ovarian surface involvements were significantly associated with inferior overall survival on univariate and continued to be statistically significant after adjustment for stage. While these clinical factors identify high risk patients, it is promising that the finding of a high incidence of HER2 in our Asian population may allow development of a HER2 targeted therapy to improve the management of mucinous ovarian cancers.
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