Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma

abstract

Highlights

•

One-third of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) have low percentage of neoplastic nuclei (PNN < 70%).

•

Higher PNN is associated with suboptimal cytoreduction and lower PNN is associated with inherited BRCA2 mutations.

•

Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

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Objective

Most molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥ 70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias.

Methods

Subjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing.

Results

PNN was < 70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P = 0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P = 0.018). Overall survival was not significantly different between subjects with < 70% or ≥ 70% PNN (median survival 51.8 vs. 46.6 months, P = 0.858).

Conclusions

One-third of HGSC has PNN < 70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

Stress and burnout among gynecologic oncologists: SGO Evidence-based Review/Recommendations

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Highlights

•

There is a high prevalence of burnout among gynecologic oncologists.

•

Physician burnout is associated with significant personal distress.

•

There are practical solutions to reduce physician burnout and promote wellness.

1. Introduction
Wellness is “a conscious, self-directed and evolving process of
achieving full potential” as defined by The National Wellness Institute
[1]. While this sounds like an aspiration for every gynecologic oncologist,
achieving it requires dedication, effort, and time, resources that
many physicians deplete at work. A career in gynecologic oncology
can be extremely rewarding, but, it is universally strenuous and
demanding. Caring for women with gynecologic cancers (and complex
gynecologic problems) requires a significant and continuous commitment
from providers which often becomes an all-encompassing mission.
Unfortunately, this level of dedication can lead to burnout [2].
Burnout is a mental state defined by any of the following three
elements: lack of enthusiasm for work, skepticism and distrust, and a
low sense of personal accomplishment. Objectively, burnout can be
measured by theMaslach Burnout Inventory,which assesses: emotional
exhaustion, depersonalization and low personal accomplishment. The
syndrome of burnout is present if at least one of the elements is significantly
abnormal [3]. In addition to burnout, physicians may also

Low-grade serous ovarian cancer: A review

abstract
 

Highlights

•

The presence of a BRAF mutation in a serous borderline tumour may protect against progression to low-grade serous cancer

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The presence of a KRAS mutation in a low-grade serous tumour may be a good prognostic factor

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The most important prognostic factor in patients with low-grade cancer is the amount of residual disease post-surgery

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Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment.

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 MEK stands for the MAPK/ERK kinase, and it is among the series of regulatory kinases targeting that pathway. It has a dual role, acting as both a serine/threonine kinase and a tyrosine kinase.

 

IBM Watson Partners With Hospitals To Fight Cancer (China/MSKCC/video)

media

 Watson for Oncology was developed by IBM with oncologists from Memorial Sloan-Kettering Cancer Center in New York and has the ability to read data from both “structured and unstructured” sources, which will be key in China given not all hospitals have electronic record systems, IBM executives said.

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IBM Watson for Oncology (see video MSKCC you tube video 2:44 min)

Primary Peritoneal Carcinoma in a BRCA1/2-negative, PALB2-positive patient

open access:
Primary Peritoneal Carcinoma in a BRCA1/2-negative, PALB2-positive patient

Highlights

• • First reported case of PPC after BSO in a BRCA1/2-negative, PALB2-positive patient
• • The PALB2 mutation and genetic counseling is discussed
• • Multi-gene panel testing can benefit prognostic factors and targeted therapy

1. Introduction

Primary Peritoneal Carcinoma (PPC) is a cancer of the abdominal peritoneal lining without involvement of the ovaries or identifiable primary tumor. Its estimated annual incidence in the United States is 0.46 per 100,000 women(Goodman et al., 2009). The actual incidence of low-grade serous PPC is much lower (< 1/150,000) (Rothacker et al., 1995). Most cases are serous subtype with cellular origin identical to that of epithelial ovarian carcinoma. PPC often mimics ovarian and fallopian tube cancers. It accounts for roughly 10% of ovarian carcinomas that have been presumably misdiagnosed (Rothacker et al., 1995).

Women undergoing prophylactic bilateral salpingo-oophorectomy (BSO) can still develop PPC years later, suggesting that certain epithelial peritoneal cancers do not originate from the ovarian surface. Instead, ovarian epithelial tumors and PPC are hypothesized to share a common embryologic origin with similar germline and somatic mutations. In current literature, nearly all PPC cases have been reported in women with a known BRCA1/2 germline mutation. However, there have been minimal studies on genetic testing outside of BRCA1/2 mutations in patients with PPC. Here, we report a case of a BRCA1/2-negative patient who had undergone prophylactic BSO and presented years later with PPC (19 years) and was subsequently found to carry a mutation in PALB2.....

Breast and Ovarian Cancer in Young Women of the Arabian Gulf Region: Relationship to Age

open access (pdf)