Assessment of Ki67 and uPA/PAI-1 expression in intermediate-risk early stage breast cancers.

BACKGROUND: The objective of this study was to compare the efficacy of biomarkers in assessing the risk of breast cancer recurrence in patients with node-negative or micrometastatic grade II breast cancer. Specifically, we compared risk assessments based on the St. Gallen clinicopathological criteria, Ki67 expression and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) expression. METHODS: This retrospective study included 347 patients with breast cancer followed at Limoges University Hospital. The optimal cut-off for high Ki67 expression (Ki67hi) was established as 20%. The threshold for uPA and PAI-1 positivity was 3 ng/mg and 14 ng/mg, respectively. RESULTS: Ki67 expression was lower in uPA/PAI-1-negative than in uPA/PAI-1-positive tumours (227 tumours; P = 0.04). The addition of Ki67 status to the St. Gallen criteria resulted in a 28% increase in the rate of identification of high-risk tumours with a potential indication for chemotherapy (P < 0.001). When considering uPA/PAI-1 levels together with the St Gallen criteria (including Ki67 expression), the number of cases identified as having a high recurrence risk with a potential indication for adjuvant chemotherapy increased by 20% (P < 0.001). Adjuvant chemotherapy was 9% less likely to be recommended by a multidisciplinary board when using the current criteria compared with using a combination of the St. Gallen criteria and Ki67 and uPA/PAI-1 status (P = 0.03). CONCLUSIONS: Taken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid.

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital.

Background: In the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy. Methods: A FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients. Results: Samples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0-86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0-117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48-2.26)]. Conclusions: This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

Maternofetal infections due to Eikenella corrodens.

Eikenella corrodens, a commensal of the human oral cavity, is generally associated with bite wounds and head and neck infections. Neonatal infections are rare. We report two cases of premature birth associated with maternofetal E. corrodens infection.

Lobular Breast Carcinoma Metastasis to the Thyroid Gland: Case Report and Literature Review.

Metastasis from primary cancer to the thyroid is uncommon in breast cancer. Here we present a case of lobular breast carcinoma that metastasized to the thyroid. A 54-year-old woman without symptoms was admitted to our institution for staging of the lymph node above the left clavicle. An 18F-fluoro-deoxy-D-glucose positron emission tomography scan was performed for staging, and low uptakes were observed in the left supraclavicular and cervical lymph nodes. High uptake was seen in the posterior and lower left lobe of the thyroid. Histologic findings indicated lobular breast carcinoma (positive GATA3, loss of E-cadherin expression) metastatic to the thyroid with a luminal profile. Immunohistochemical analysis was negative for primary thyroid or parathyroid carcinoma. To our knowledge, this is the first report of a patient presenting a metastatic invasive lobular carcinoma in the thyroid and lymph nodes without a prior diagnosis of breast cancer.

Interest of postmortem-collected specimens in the diagnosis of fulminant meningococcal sepsis.

We reported the case of a child who died of purpura fulminans. The diagnosis of Neisseria meningitidis serogroup C could be assessed using postmortem specimens collected up to 10 h after death. We were able to identify the bacteria by culture and/or PCR on samples without having autopsy performed. Soluble antigens were also detected in serum.

[Peritoneal pseudo-carcinosis in a young woman: peritoneal gliomatosis]. / Une pseudo-carcinose péritonéale de la jeune femme: la gliomatose péritonéale.

Gliomatosis peritonei is a peritoneal colonization of glial cells producing nodules similar to peritoneum carcinosis. Gliomatosis is often associated with ovarian teratoma. We describe a case of gliomatosis 8 years after the removal of a mature ovarian teratoma. The physiopathology, treatment and medical follow up of this benign disease is discussed.

Adjuvant chemotherapy in node-negative breast cancer: UPA/PAI-1 determinations for 163 cases.

BACKGROUND: The urokinase-type plasminogen activator (UPA) and its main inhibitor plasminogen activator inhibitor-1 (PAI-1) are involved in tumor interactions with the microenvironment. The UPA/PAI-1 content in tumor tissue can be used to identify populations at low-or high-risk of recurrence of breast cancer, even without other standard prognostic markers. MATERIALS AND METHODS: The purpose of the present study was to compare adjuvant chemotherapy decisions made by a multi-disciplinary board for 163 node-negative breast cancer cases, based on clinicopathological (CP) and UPA/PAI-1 risk assessment. RESULTS: The UPA/PAI-1 levels identified 37% of the population as being at low risk. Adjuvant chemotherapy indication was spared in high-CP risk in 17%, but maintained in low-CP risk in 33%. CONCLUSION: The use of UPA/PAI-1 data did not consistently result in a decrease of adjuvant chemotherapy. This study highlighted the difficulties encountered in a local multi-disciplinary board in determining appropriate roles and weights of new prognostic markers (UPA/PAI-1 was not routinely employed in France) when no data are available for assessing their prognostic and predictive power compared to other prognostic factors.

Lymph node assessment with (18)F-FDG-PET and MRI in uterine cervical cancer.

BACKGROUND: To assess pelvic (P) and/or paraaortic (PA) lymph node (LN) involvement in patients with primary stage IA-IVA cervical cancer, (18)F-fluorodeoxyglucose (FDG)-PET, and MRI were compared with histological results. MATERIALS AND METHODS: Forty patients were prospectively evaluated. Twenty-eight patients underwent radio-chemotherapy (RT-CT) after initial staging and lymph node dissection (LND). RESULTS: PLN metastases were present in 6/31 patients. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and accuracy in detecting PLN metastases were 67%, 84%, 50%, 91% and 81%, with MRI, and 33%, 92%, 50%, 85% and 81%, with FDG-PET. PALN metastases were present in 5/27 patients. Sensitivity, specificity, PPV, NPV and accuracy were 60%, 73%, 33%, 89% and 70% with MRI and 100%, 77%, 50%, 100% and 81% with FDG-PET in detecting PALN metastasis. CONCLUSION: FDG-PET is less accurate than MRI for PLN, but more accurate for PALN; FDG-PET cannot replace PA surgical procedures, but could guide them.

[Pathological characteristics in screening versus clinically-detected breast cancer]. / Caractéristiques anatomopathologiques des cancers du sein dépistés versus diagnostiqués hors dépistage.

We report pathological characteristics of screen detected breast cancers versus breast cancers diagnosed outside the official breast screening program. The breast cancer screening program was organised in the county of Haute-Vienne and a pathological record was established in the Association de dépistage des cancers du sein (ADCS 87). Three hundred and thirty three cases were recorded in 50 to 74 years-old women who had been screened (74 were interval cancers), six hundred and eighty seven in 50 to 74 years-old women without screening and three hundred and fifteen in women under 50. No difference in ductal carcinoma in situ or histological type was noted but tumor size and lymph node involvement presented significantly more favorable prognosis in screen detected breast cancers. This study confirms the potential benefit of screening in breast cancer.

Streptococcus porcinus as a cause of spontaneous preterm human stillbirth.

We report, to our knowledge, on the first case of a woman suffering stillbirth due to Streptococcus porcinus on the basis of microbiologic and histologic data.

Two unusual chromosome aberrations ascertained by sonographic anomalies.

We describe two cases of sonographic abnormalities associated with unusual chromosomal aberrations. Case 1 presented with a cystic hygroma at 12 weeks' gestation. Cytogenetic analysis revealed an unbalanced complex chromosome rearrangement implicating chromosomes 6, 13 and 21 (karyotype: 47,XX,t(6;21;14)(q14;q21;q21)mat,+21) and corresponding to a complete trisomy 21. This anomaly resulted from malsegregation of a maternal balanced three-way translocation. For case 2, an alobar holoprosencephaly was identified by ultrasonography at 23 weeks' gestation. Chromosomal analysis showed a recombinant rec (13), dup q chromosome, secondary to unequal crossing-over of a paternal pericentric inversion of chromosome 13, giving rise to partial trisomy 13q (karyotype: 46,XX,rec(13)dup(13q)inv(13)(p11q21)pat). These two cases illustrate the role of ultrasound in leading to detection not only of foetal chromosomal aberrations but also of rare balanced chromosomal rearrangements presented by one of the two parents.