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AIMS - Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized.
METHODS AND RESULTS - We reviewed the clinicopathological and molecular features of 42 CRC with MP features. Twenty-nine cases were also evaluated for immunohistochemical evidence of epithelial-mesenchymal transition (EMT). The extent of MP features within our cohort ranged from 5% (13 cases) to 100% (one case). Twenty-seven cases featured prominent cribriforming with dirty necrosis in the non-MP component; nine displayed mucinous features. Twenty-four of 29 cases (83%) demonstrated evidence of EMT. Thirty-six cases (86%) showed advanced T-category (pT3 or pT4), 31 (74%) had lymph node metastases and 23 (55%) had distant metastases. Median overall follow-up was 36 months. Seventeen patients (40%) died of disease, with median survival of 23 months. Mutations were seen in 17 of 31 tested cases (55%), including 11 KRAS mutations and four BRAF V600E mutations. Microsatellite instability testing was performed on 21 cases; all were microsatellite-stable. Compared to a cohort of 972 conventional CRC, MP CRC was more likely to present as stage IV disease (P < 0.001), but patients with MP CRC showed no significant differences in overall survival after adjusting for stage.
CONCLUSIONS - Micropapillary features in CRC portend a high likelihood of advanced local disease and distant metastases. MP CRC is often associated with a cribriform pattern elsewhere in the tumour and cystic nodal metastases with prominent necrosis. They also show frequent mutations in KRAS and BRAF. Immunohistochemical evidence of EMT is common in MP CRC.
© 2016 John Wiley & Sons Ltd.
Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case-control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n = 21) from the healthy controls (n = 35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high-throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection.
PURPOSE - Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial carcinoma. The majority of patients with clinical Stage I UPSC are found to have extrauterine disease at the time of surgery. Most authors report survival rates of 35-50% for Stage I-II and 0-15% for Stage III and IV UPSC. Surgical treatment as the sole therapy for patients with Stage I-IV UPSC is unacceptable because of high recurrence rates. Chemotherapy, radiotherapy, or both have been added after surgery in an attempt to improve survival. However, the survival benefit to patients from such multimodality therapy remains uncertain. This study analyzes the patterns of failure in patients with FIGO Stages I-IV UPSC treated by multimodality therapy.
METHODS AND MATERIALS - Forty-two women with FIGO Stages I-IV UPSC who were treated by multimodality therapy were analyzed retrospectively between 1988 and 1998. Data were obtained from tumor registry, hospital, and radiotherapy chart reviews, operative notes, pathology, and chemotherapy flow sheets. All the patients underwent staging laparotomy, peritoneal cytology, total abdominal hysterectomy and salpingo oophorectomy, pelvic and para-aortic lymph node sampling, omentectomy, and cytoreductive surgery, when indicated followed by radiotherapy and/or chemotherapy. Therapy consisted of external beam radiation therapy in 11 patients (26%), systemic chemotherapy in 20 (48%), and both radiotherapy and chemotherapy in 11 (26%). The treatments were not assigned in a randomized fashion. The dose of external beam radiation therapy ranged from 45-50.40 Gy (median 45). Of the 31 patients (74%) who received chemotherapy, 18 received single-agent (58%), whereas 13 received multiagent chemotherapy (42%).
RESULTS - Median follow-up for all patients was 19 months (range 4-72). Median follow-up for the surviving patients was 36 months (range 21-72). Their median age was 65 years. Six patients (14%) had Stage I, 8 patients (19%) had Stage II, 10 (24%) had Stage III, and 18 (43%) had Stage IV disease. Twenty-nine patients (69%) had suffered recurrence at the time of last follow-up. The actuarial failure rate at 2 and 5 years was 58% and 67%, respectively. The majority of the patients (19/29) recurred in the abdomen, vagina, or pelvis (66%). Metastases outside the abdomen were much less common as the first site of failure (17%). Twenty-five patients (60%) had died at the time of reporting; the observed survival rate at 2 years and 5 years was 52% and 43%, respectively.
CONCLUSIONS - Our data suggest that, after multimodality therapy of FIGO Stage I-IV UPSC, most patients developed abdominopelvic (locoregional) failure, and the great majority of the failures occurred in the abdomen, vagina, and pelvis (66%). Abdominopelvic failure as a component of distant failure occurred in an additional 5 patients (17%). Distant failure alone occurred in 17% of the patients.We propose that future studies should combine whole abdominal radiotherapy (WART) with pelvic and vaginal boosts, in addition to chemotherapy for FIGO Stage I-IV UPSC, especially in patients with minimal residual disease, to attempt to improve the dismal prognosis of patients with UPSC.
Many malignancies appear to occur with increased frequency and aggressive patterns of spread in patients seropositive for human immunodeficiency virus (HIV). The relationship between HIV infection and cervical neoplasia suggests that these patients present with more advanced disease and demonstrate poor response to therapy. To date, there have been no reported cases of ovarian cancer with concomitant HIV infection. We describe a young, gravid woman with an advanced ovarian carcinoma diagnosed at the time of delivery. Following poor response to cytoreductive surgery and initial chemotherapy, she was found to be HIV-seropositive. She received multiple chemotherapeutic regimens and experienced significant complications associated with her treatment and HIV infection. She progressively deteriorated and died within 13 months of diagnosis. Based on these findings and experience with other HIV-associated malignancies, it is apparent that the conventional approach to therapy is inadequate to treat the advanced and more aggressive form of disease seen in women infected with HIV.