Sentinel node mapping in a pregnant woman with cervical cancer: a case report

The possibility of reducing morbidity associated with surgical dissection while maintaining accurate tumor staging is one of the greatest advantages of the sentinel node approach in surgical oncology. The sentinel node mapping has already proven to be useful in melanoma, breast cancer, and vulvar cancer. We report the first case of sentinel node detection by technetium-labeled radiocolloid in a pregnant woman with cervical cancer. The histologic analysis of the operative specimen showed a poorly differentiated squamous carcinoma with metastasis in the sentinel node and a neoplasic embolus in a blood vessel of the placental bed. The lymphatic mapping and sentinel lymph node detection are feasible during pregnancy.

Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

Aims Endometrial cancer is one of the most common cancers in women worldwide, but there is a lack of diagnostic markers for early detection of these tumours. The raf kinase inhibitory protein (RKIP) negatively regulates the Raf/MEK/ERK pathway, and the downregulation of RKIP is associated with tumour progression and metastasis in several human neoplasms. The aim of this study was to assess the expression levels of RKIP in endometrial cancer and determine whether this expression correlates with clinical outcome in these patients.Methods Tissue microarrays constructed using tissue samples from 209 endometrial adenocarcinomas, 49 endometrial polyps and 48 endometrial hyperplasias were analysed for RKIP expression by immunohistochemistry.Results The authors found that RKIP expression decreases significantly during malignant progression of endometrial cancer; it is highly expressed in non-neoplastic tissues (polyps 79.6%; hyperplasias 87.5%) and expressed at very low levels in endometrioid adenocarcinomas (29.7%). No correlations were observed between RKIP expression, clinicopathological data and survival.Conclusion This study demonstrated for the first time that RKIP expression is lost during the carcinogenic evolution of endometrial tumours and that the loss of RKIP expression is associated with a malignant phenotype. Functional studies are needed to address the biological role of RKIP downregulation in endometrial cancer.

HPLC-EICD: An Useful Tool for the Pursuit of Novel Analytical Strategies for the Detection of Antioxidant Secondary Metabolites

Living cells are continuously exposed to a variety of challenges that exert oxidative stress and are directly related with senescence and the onset of various pathological conditions such as coronary heart disease, rheumatoid arthritis and cancer. Nevertheless, living organisms have developed a complex antioxidant network to counteract reactive species that are detrimental to life. With the aim of bio-prospecting plant species from the Brazilian Cerrado and Atlantic Forest, we have established a methodology to detect secondary antioxidant metabolites in crude extracts and fractions obtained from plant species. Combining HPLC with an electrochemical detector allowed us to detect micromolecules that showed antioxidant activities in Chimarrhis turbinata (DC) leaf extracts. Comparison with purified flavonoid standards led us to identify the compounds in their natural matrices giving valuable information on their antioxidant capacity.

Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER-2 by immunohistochemistry in breast carcinoma

Aims: To evaluate the reliability of fine needle aspirate cell blocks in the assessment of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins by immunohistochemistry in comparison with surgical specimens. Materials and methods: This is a retrospective study of 62 cases of breast carcinoma diagnosed by fine needle aspiration cytology (FNAC) and confirmed using the surgical specimen. Immunohistochemical tests were performed to assess the presence of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins in cell blocks and the corresponding surgical specimens. The cell block method used alcohol prior to formalin fixation. Cases with 10% or more stained cells were considered positive for ER and PR. Positivity for HER-2/neu was assessed on a scale of 0-3+. The criterion for positivity was a score of 3+. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the cell blocks in the investigation of ER, PR and HER-2/neu protein (3+) were (%): ER, 92.7, 85.7, 92.7, 85.7 and 90.3; PR, 92.7, 94.7, 97.4, 87.0 and 93.5; HER-2/neu, 70.0, 100.0, 100.0, 94.5 and 95.2. Discrepancies were seen in cell blocks in the 1+ and 2+ HER-2/neu staining scores: two of 12 cases scoring 2+ and one case of 26 scoring 1+ on cell blocks scored 3+ on surgical specimens. The correlation index between cell block and corresponding surgical specimen varied from 90% to 94%. Conclusion: Cell blocks provide a useful method of assessing ER, PR and HER-2/neu, mainly for inoperable and recurrent cases, but consideration should be given to carrying out FISH analysis on 1+ as well as 2+ HER-2/neu results. © 2012 Blackwell Publishing Ltd.

Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?

A significant proportion (up to 62) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68), 9q34.13 (64), 21q22.3 (60), 6p21 and 6q25 (56) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48). DNA losses were observed in 20 of samples and mainly detected on 5q31.2 (35), 16p13.2 (30), 9q33.1 and 9q33.29 (25) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70 of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Proteinprotein interaction networks were created to identify possible pathways associated with OSCC progression.

Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevalence of the germline TP53 p.R337H mutation in families with multiple cases of cancer

Germline mutations in TP53 gene are associated with Li-Fraumeni syndrome (LFS) and its variants Li-Fraumeni-like (LFL). They predispose carriers to a wide variety of early onset tumors. In Brazil, there is a high frequency of a germline mutation in this gene (NC_000017.9: c.1010G>A; p.R337H) in Southern and Southeastern regions, due to a founder effect. It is estimated to be present in 0,3% ofthe local population, but only few families have been detected. Due to this significant divergence, the purpose of this study was to verify the effectiveness of wider criteria for detection of these individuals. Herein, clinical criteria were established, DNA samples were collected, analyzed by Restriction Fragment Length Polymorphism (RFLP) and sequenced. Thus, assessing the prevalence of this mutation in families with multiple cases of cancer. Based on our proposed criteria, one out of 31 patients (3,22%) was found to carry p.R337H mutation. The patient developed ductal invasive breast cancer at age 47, invasive adenocarcinoma of the lung at age 48 and soft-tissue sarcoma at age 49. In addition, an extensive cancer family history was referred, atypical for LFS, including a case of Ewing’s sarcoma. These outcomes indicate that the proposed criteria may detect probable carriers who did not fit previous LFS criteria. Nevertheless, additional studies, which might include a larger number of families and more stringent parameters, will be useful to improve screening sensibility

Phospho-mTOR in non-tumour and tumour bladder urothelium: Pattern of expression and impact on urothelial bladder cancer patients

Urothelial bladder carcinoma (UBC) is heterogeneous in its pathology and clinical behaviour. Evaluation of prognostic and predictive biomarkers is necessary, in order to produce personalised treatment options. The present study used immunohistochemistry to evaluate UBC sections containing tumour and non-tumour areas from 76 patients, for the detection of p-mTOR, CD31 and D2-40 (blood and lymphatic vessels identification, respectively). Of the non-tumour and tumour sections, 36 and 20% were scored positive for p-mTOR expression, respectively. Immunoexpression was observed in umbrella cells from non-tumour urothelium, in all cell layers from non-muscle-invasive (NMI) tumours (including expression in superficial cells), and in spots of cells from muscle-invasive (MI) tumours. Positive expression decreased from non-tumour to tumour urothelium, and from pTl/pTis to pT3/pT4 tumours; however, the few pT3/pT4 positive cases had worse survival rates, with 5-year disease-free survival being significantly lower. Angiogenesis occurrence was impaired in pT3/pT4 tumours that did not express p-mTOR. In conclusion, p-mTOR expression in non-tumour umbrella cells is likely a reflection of their metabolic plasticity, and extension to the inner layers of the urothelium in NMI tumours is consistent with an enhanced malignant potential. The expression in cell spots in a few MI tumours and absence of expression in the remaining tumours is intriguing and requires further research. Additional studies regarding the up- and downstream effectors of the mTOR pathway should be conducted.

Association between concurrent genital bleeding and cervical cancer: a cross-sectional study

Genital bleeding may be a common symptom among women with cervical cancer. Cross-sectional study evaluating whether the prevalence of cervical smear results is different in women with and without clinical information about concurrent genital bleeding. The sample consisted of 2 324 836 smears; of these, 0.4% had clinical information on genital bleeding. When stratified by age group, women with genital bleeding had a higher chance of a cytological result of a high-grade squamous intraepithelial lesion [30-49 years odds ratio (OR) 2.38; 95% confidence interval (CI) 1.60-3.53 and ≥50 years OR 6.30; 95%CI 3.72-10.67), of squamous cell carcinoma (SCC) (30-49 years OR 24.70; 95%CI 11.96-51.03 and ≥50 years OR 48.91; 95%CI 31.28-76.47) and of atypical glandular cells (30-49 years OR 5.72; 95%CI 3.30-9.93 and ≥50 years OR 11.56; 95%CI 5.96-22.45); there was also a higher chance of adenocarcinoma for women ≥50 years (OR 53.13; 95%CI 28.08-100.51). The sensitivity of genital bleeding for women aged 18-29 years was 0.4% for high-grade squamous intraepithelial lesion (HSIL); for women 30-49 years old the rate was 0.9% for HSIL, 8.6% for SCC and 2.1% for atypical glandular cells of undetermined significance (AGUS), while for women aged from 50 years or more the rates were 2.0% for HSIL, 13.7% for SCC, 3.6% for AGUS and 14.7% for adenocarcinoma. Women ≥30 years old with genital bleeding should be referred for colposcopy to rule out the possibility of cervical cancer.

Low expression of human histocompatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis, associated with Papilloma Virus (HPV)

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICCW)] and absence [ICC without metastasis (ICCWT)] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICCWT (n=52 patients) and ICCW (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.