Implementation of endometrial cancer molecular subtyping into a hybrid community-academic practice.

OBJECTIVES: We sought to confirm utility of our institution's modified Proactive Molecular Risk Classifier for Endometrial Cancer protocol in our daily practice, which includes mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) immunohistochemistry with in-house next-generation sequencing for POLE, TP53, and CTNNB1. METHODS: We conducted a retrospective review of all patients in our institution who underwent primary endometrial carcinoma resection from the year prior to protocol implementation (PRE; October 1, 2020, to September 30, 2021) through first year of implementation (POST; October 1, 2021, to September 30, 2022) to compare the distribution of molecular and traditional staging factors using GOG-249 criteria to assign clinical risk. RESULTS: In total, 136 of 260 PRE patients were classified as clinically low risk (LR), of whom 31 were MMR deficient. Of the 157 LR POST patients with endometrioid-type carcinoma, 45 were MMR deficient, 5 were POLE mutant, 5 were TP53 mutant, 56 were of no specific molecular profile (NSMP), and 46 did not receive full protocol testing. Of all 79 POST NSMP endometrioid-type cases, 18 were CTNNB1 mutated and 8 showed L1CAM expression. CONCLUSIONS: Our protocol identified 22 (14%) of 157 LR tumors that harbored incipient intermediate- to high-risk molecular aberrations in TP53, CTNNB1, or L1CAM. Moving forward, results of ongoing trials assessing adjuvant therapy decisions based on molecular classification are necessary to confirm protocol utility and identify appropriate modifications.

Selective breast/gynecologic pathology fellowship training in the United States: Experience of program directors.

Published data on combined breast and gynecologic [breast/gyn] surgical pathology fellowship training programs are limited. Our study aimed to survey the landscape of such fellowships in the United States (US), including specific information about their characteristics and the educational activities therein. Using web searches, we identified programs offering combined breast/gyn surgical pathology fellowship training. We developed a 26-item questionnaire asking program directors to report on the characteristics of their fellowship training structure. The search revealed 25 academic based programs offering one-year combined breast/gyn fellowship training, predominantly located (40 %) in the Northeast area. The following data was obtained: 44 % of the programs were accredited by the ACGME, 82 % required >19 weeks of breast and gyn service, and 69.6 % accepted the common application, 54.5 % of programs require completion of a research project for graduation. An annual average of 3000 breast and 3000 gyn cases appears to be the usual volume of cases. Interestingly, only 36 % of the program directors are graduates of a combined breast/gyn fellowship program. In conclusion, we present the most comprehensive and up-to-date census of combined breast/gyn pathology fellowships in the US. Our study provides valuable information on the current state of combined breast/gyn pathology fellowship training. The information will be helpful to current and prospective trainees, as well as program leaders.

Immunohistochemistry and immunofluorescence utilization audit by subspecialty in an academic setting: A step toward stewardship.

There are immunohistochemistry (IHC) and immunofluorescence (IF) panels described in the literature and established by personal and institutional experiences that are in common use by pathologists in their daily practice. Stewardship is a difficult discussion because IHC utilization is influenced by many factors including the pathologist's experience, background, practice setting, personal bias, and medicolegal culture. We developed the methodology to audit the IHC/IF utilization in our academic subspecialty practice. We aim to share this methodology and to provide our data that can be used for consideration by other subspecialized academic practices. This analysis included a total of 63,157 specimens that were accessioned during 2022, representing 38,612 cases. The likelihood of ordering IHC/IF ranged from 1 % (in genitourinary pathology) to 59 % (in renal pathology). The average percentage of specimens with IHC/IF was 21 % for the entire practice. In cases where IHC/IF was ordered, the number of stained slides averaged 4.9 per specimen for the entire practice. The number of IHC/IF slides per specimen ranged from 1.9 (in gastrointestinal pathology) to 12.2 (in renal pathology). The highest number of antibodies ordered for a single specimen by subspecialty ranged from 11 (in cardiac pathology) to 63 (in dermatopathology). Renal pathology was the only subspecialty that had an average number of IHC/IF slides that was statistically significantly different from all other subspecialties. We described the various patterns of utilization by subspecialty and rationalized their subtle differences. We also analyzed the types of cases that exceeded the reimbursement limits set by the Centers for Medicare and Medicaid Services (CMS).

Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Histopathologic Features of Breast Tissue From Transgender Men and Their Associations With Androgen Therapy.

OBJECTIVES: To assess the histopathologic features of breast tissue of transgender men (TM) undergoing gender-affirming bilateral mastectomies in relation to androgen therapy (AT). METHODS: We reviewed 374 transgender bilateral mastectomy cases from 2017 to 2020. Of these, 314 (84.4%) patients received preoperative AT. We compared these with 127 cases of cisgender females undergoing elective breast reduction. RESULTS: Breast specimens from TM on AT, compared with cisgender women, showed a median higher gross percentage of fibrous tissue (P < .001), reduced lobular density (P = .004), higher amount of lobular atrophy (P < .001), and lower incidence of cysts (P < .001), apocrine metaplasia (P < .001), calcifications (P < .001), columnar cell change (P = .002), and atypia (P = .003). Each additional month of AT was associated with a 2% decrease in the odds of having nonapocrine cysts (P = .02), a 5% decrease in the odds of having usual ductal hyperplasia (P = .007), and a 0.14% decrease in median lobular density (95% confidence interval, -0.18 to -0.05). CONCLUSIONS: In this study, breast specimens from TM, particularly with a history of AT, had a higher proportion of fibrous tissue, fewer lobules, and a higher degree of lobular atrophy than cisgender females. Rare cases of atypia were not predicted by preoperative imaging or gross findings, supporting routine microscopic evaluation of these specimens.

Mixed neuroendocrine/Non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma.

•Mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma is extremely rare.•It is important to differentiate the gastrointestinal-type adenocarcinoma arising along with neuroendocrine tumor from a primary mucinous adenocarcinoma of the ovary. SATB2 and CDX2 Immunohistochemical stains play important role in differentiate these two.•This case highlights the careful morphologic evaluation and extensive sampling is crucial to make this rare diagnosis.

Microscopic Features of Vaginectomy Specimens from Transgender Patients.

OBJECTIVES: We aimed to better understand the histologic changes in vaginectomy specimens in transgender and gender-diverse (TGD) individuals after prolonged androgen administration. METHODS: After obtaining institutional review board approval, we reviewed clinical records for all TGD individuals who underwent vaginal tissue resection at our institution between January 2002 and July 2020. RESULTS: Ten transgender males who underwent vaginectomy for gender affirmation were identified. All patients had been assigned female gender at birth, and the median age at surgery was 41 years (range, 22-74 years). All 10 patients had received androgen for 2 to 10 years preoperatively. The corresponding pathology specimens were examined grossly and microscopically, including with immunohistochemical stains for NKX3.1, prostate-specific antigen (PSA), p501s, and androgen receptor (AR). No gross lesions were identified. Microscopically, prostate-like glands (8/10), urothelial metaplasia (4/10), and vaginal atrophy (8/10) were identified. Seven cases with prostate-like glands showed positive staining with PSA, NKX3.1, p501s, and AR in both squamous and glandular components. CONCLUSIONS: Recognition of these androgen-related changes enables pathologist to avoid the overdiagnosis of dysplasia. Long-term follow-up is needed to thoroughly understand any potential future implications of these androgen-related changes.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.

Standardizing Pathologic Evaluation of Breast Carcinoma After Neoadjuvant Chemotherapy.

CONTEXT.­: Neoadjuvant systemic therapy refers to the use of systemic agent(s) for malignancy prior to surgical treatment and has recently emerged as an option for most breast cancer patients eligible for adjuvant systemic therapy. Consequently, treated breast carcinomas have become routine specimens in pathology practices. A standard protocol has not yet been universally adopted for the evaluation and reporting of these specimens. The American Joint Committee on Cancer staging system recognizes the challenges in staging breast carcinomas after neoadjuvant treatment and provides important data points but does not currently provide detailed guidance in estimating the residual tumor burden in the breast and lymph nodes. The Residual Cancer Burden system is the only Web-based system that quantifies treatment response as a continuous variable using residual tumor burden in the breast and the lymph nodes. OBJECTIVE.­: To provide clarifications and guidance for evaluation and reporting of postneoadjuvant breast specimens, discuss issues with the current staging and reporting systems, and provide specific suggestions for future modifications to the American Joint Committee on Cancer system and the Residual Cancer Burden calculator. DATA SOURCES.­: English-language literature on the subject and the data from the I-SPY 2, a multicenter, adaptive randomization phase 2 neoadjuvant platform trial for early-stage, high-risk breast cancer patients. CONCLUSIONS.­: This article highlights challenges in the pathologic evaluation and reporting of treated breast carcinomas and provides recommendations and clarifications for pathologists and clinicians. It also provides specific recommendations for staging and discusses future directions.

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

IMPORTANCE: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01042379.

Sentinel Nodal Metastasis Detection in Endometrial Carcinoma With Microcystic, Elongated, and Fragmented (MELF) Pattern by Cytokeratin Immunostaining.

OBJECTIVES: The microcystic, elongated, and fragmented (MELF) pattern of myoinvasion in endometrial carcinoma (EC) is associated with an increased risk of lymph node metastasis. Our aim is to assess the role of cytokeratin immunohistochemical (IHC) stains in detecting sentinel nodal metastasis in MELF pattern tumors. METHODS: We recovered 19 MELF pattern EC hysterectomies with lymphadenectomy from our files. Negative nodes were subjected to cytokeratin AE1/AE3 IHC. Ten additional cases with sentinel lymph node (SLN) biopsies primarily assessed by IHC were also analyzed. RESULTS: Of the 19 cases of EC, 6 had positive lymph nodes based on H&E-stained sections at the time of their initial diagnosis. With the addition of IHC stains, 8 previously negative cases were found to have node metastases, and 3 of these were SLNs. Among the 10 cases primarily assessed by IHC, 5 had malignant cells in their SLNs. CONCLUSIONS: Cytokeratin IHC staining detected malignant cells in 9 of 16 cases with SLNs in our sample of women with MELF pattern of myoinvasion. Immunohistochemical stains should be routinely performed on SLNs from all MELF-positive cases to detect occult lymph node metastases and isolated tumor cells.

Synchronous breast carcinoma and peritoneal mesothelioma.

Breast cancer may be associated with other primary cancers via germline mutations; however, sporadic occurrences of other malignancies are rare. With increased use of advanced breast cancer imaging, including MRI and PET/CT, other incidental synchronous cancers are increasingly identified. Such cases can represent unique diagnostic and treatment challenges. Here, we present a case of a young woman diagnosed with primary breast cancer who underwent imaging studies identifying an incidental primary peritoneal mesothelioma.

Left bundle branch block revealing a primary small bowel carcinoid metastasizing to the interventricular septum.

Carcinoid tumours of the heart occur most commonly as a result of metastatic disease and usually affect the right side of the heart. We report a case of a solitary carcinoid metastasis to the interventricular septum without hepatic involvement in a 74-year-old man.

Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial.

Importance: Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in the context of a phase 2 neoadjuvant platform trial. Objective: To evaluate the association of pCR with event-free survival (EFS) and pCR with distant recurrence-free survival (DRFS) in subpopulations of women with high-risk operable breast cancer treated with standard therapy or one of several novel agents. Design, Setting, and Participants: Multicenter platform trial of women with operable clinical stage 2 or 3 breast cancer with no prior surgery or systemic therapy for breast cancer; primary tumors were 2.5 cm or larger. Women with tumors that were ERBB2 negative/hormone receptor (HR) positive with low 70-gene assay score were excluded. Participants were adaptively randomized to one of several different investigational regimens or control therapy within molecular subtypes from March 2010 through 2016. The analysis included participants with follow-up data available as of February 26, 2019. Interventions: Standard-of-care neoadjuvant therapy consisting of taxane treatment with or without (as control) one of several investigational agents or combinations followed by doxorubicin and cyclophosphamide. Main Outcomes and Measures: Pathologic complete response and 3-year EFS and DRFS. Results: Of the 950 participants (median [range] age, 49 [23-77] years), 330 (34.7%) achieved pCR. Three-year EFS and DRFS for patients who achieved pCR were both 95%. Hazard ratios for pCR vs non-pCR were 0.19 for EFS (95% CI, 0.12-0.31) and 0.21 for DRFS (95% CI, 0.13-0.34) and were similar across molecular subtypes, varying from 0.14 to 0.18 for EFS and 0.10 to 0.20 for DRFS. Conclusions and Relevance: The 3-year outcomes from the I-SPY2 trial show that, regardless of subtype and/or treatment regimen, including 9 novel therapeutic combinations, achieving pCR after neoadjuvant therapy implies approximately an 80% reduction in recurrence rate. The goal of the I-SPY2 trial is to rapidly identify investigational therapies that may improve pCR when validated in a phase 3 confirmatory trial. Whether pCR is a validated surrogate in the sense that a therapy that improves pCR rate can be assumed to also improve long-term outcome requires further study. Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.

Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. METHODS: This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. RESULTS: One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84-6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04-3.88; p = .039) compared to HER2-negative tumors. CONCLUSIONS: Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

Real-Time Intraoperative Consultation Reporting in the Electronic Health Record.

OBJECTIVES: We sought to make pathologists' intraoperative consultation (IOC) results immediately available to the surgical team, other clinicians, and laboratory medicine colleagues to improve communication and decrease postanalytic errors. METHODS: We created an IOC report in our stand-alone laboratory information system that could be signed out prior to, and independent of, the final report, and transfer immediately to the electronic health record (EHR) as a preliminary diagnosis. We evaluated two metrics: preliminary (IOC) result review in the EHR by clinicians and postanalytic errors. RESULTS: We assessed 2,886 IOC orders from the first 22 months after implementation. Clinicians reviewed 1,956 (68%) of the IOC results while in preliminary status, including 1,399 (48%) within the first 24 hours. We evaluated 150 cases preimplementation and 300 cases postimplementation for discrepancies between the pathologist's IOC result and the IOC result recorded by the surgeon in the operative note. Discrepancies dropped from 12 of 150 preimplementation to 6 of 150 and 7 of 150 in postimplementation years 1 and 2. One of the 25 discrepancies had a major clinical impact. CONCLUSIONS: Real-time reporting of IOC results to the EHR reliably transmits results immediately to clinical teams. This strategy reduces but does not eliminate postanalytic interpretive errors by clinical teams.

Intraoperative inking is superior to suture marking for specimen orientation in breast cancer.

Margin status is an important indicator of residual disease after breast-conserving surgery (BCS). Intraoperatively, surgeons orient specimens to aid assessment of margins and guide re-excision of positive margins. We performed a retrospective review of BCS cases from 2013 to 2017 to compare the two specimen orientation methods: suture marking and intraoperative inking. Patients with ductal carcinoma in situ, T1/T2 invasive cancer treated with BCS were included. Rates of positive margins and residual disease at re-excision were evaluated. 189 patients underwent BCS; 83 had suture marking, 103 had intraoperative inking and 3 had un-oriented specimens. The incidence of positive margins was 29% (24 patients) in the suture marked group and 20% (21 patients) in the intraoperative inked group (P = .18). Among the 45 patients with positive margins, 60% of tumors were stage T1, 76% were node negative, 36% were palpable with median tumor size of 1.5 cm. Residual disease was identified on re-excision in 21% of the suture marked specimens and 57% of intraoperative inked specimens (P = .028). The incidence of residual cancer at re-excision for positive margins was higher for intraoperatively inked versus suture marked specimens. This finding suggests that intraoperative inking is more effective at guiding re-excision of positive margins.

Adenomyosis As a Confounder to Accurate Endometrial Cancer Staging.

The coexistence of endometrial adenocarcinoma and adenomyosis in the same uterus is a common phenomenon. In many of such affected patients foci of adenomyosis could also be colonized by adenocarcinoma. The various permutations arising from these scenarios pose preoperative imaging and postoperative pathologic staging challenges. This article aims to raise awareness of these staging issues and lists some of the relevant practical approaches. Adenomyosis reduces the accuracy of magnetic resonance imaging in assessing the depth of invasion as it reduces the contrast between the endometrial cancer adenomyosis-involved myometrium. The article also offers an alternate argument for staging cancers where myoinvasion is found deep in the myometrium, arising from cancer-positive adenomyotic foci when the surface tumor is either limited to the endometrium or to the inner half of myometrium.

Analysis of Differentially Expressed MicroRNAs and Circulating Tumor Cells as Predictive Biomarkers of Platinum Chemoresistance in Primary Ovarian Carcinomas: A Prospective Study.

LESSON LEARNED: Circulating tumor cells, microRNA markers, or other biomarkers merit examination as part of correlative scientific analyses in prospective clinical trials. BACKGROUND: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma; however, no biomarkers of ovarian carcinoma chemoresistance have been validated. We performed a prospective trial designed to identify tumor-based predictive biomarkers of platinum resistance. METHODS: Tumor specimens were collected from 29 women with newly diagnosed histopathologically proven primary ovarian carcinoma. Of these, 23 women had specimens accessible for assessment and outcome data available regarding chemosensitive versus chemoresistance status via review of the medical record. Tumor slices were stained with antibodies against two microRNAs (miRNAs 29b and 199a) differentially expressed in chemoresistant ovarian cancer cell lines. Additionally, blood samples obtained at the time of diagnosis were analyzed for the presence of circulating tumor cells (CTCs). RESULTS: The average age of the patients was 64 years, and 82.6% had high-grade epithelial carcinomas. The baseline median CA-125 was 464 (range 32-2,782). No statistically significant differences were observed in miR29b or 199a expression in platinum-resistant/refractory versus platinum-sensitive tumors. Furthermore, the presence of CTCs was not found to be statistically significantly predictive of eventual platinum resistance. CONCLUSION: Our analysis showed no differences in miR29b and 199a expression, and differences in baseline CTCs in women with newly diagnosed ovarian tumors were not statistically significant.