Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia

Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16INK4a (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

Sandstorm Appearance of Pulmonary Alveolar Microlithiasis Incidentally Detected in a Young, Asymptomatic Male

Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM.

Cytokeratin immunoreactivity in Ewing sarcoma/ primitive neuroectodermal tumour

Ewing sarcoma (ES)/ primitive neuroectodermal tumour (PNET) is an aggressive malignant neoplasm affecting mainly children and young adults. The tumour is included with other primitive neoplasms under the category of small round cell tumour. Cytokeratin expression in ES/PNET has been described in sporadic case reports as well as a few systemic series. We studied this feature in Malaysian patients diagnosed in University Malaya Medical Centre on the basis of typical morphology and immunohistochemical assays. Immunohistochemical staining for AE1/AE3 and MNF116 were performed in 43 cases. Cytokeratin was expressed in 17 cases (39.5%) in focal, intermediate or diffuse patterns. There was no significant association between cytokeratin immunoreactivity and the following parameters: patient age, sex, skeletal and extraskeletal primary location as well as primary, metastastic or recurrent tumours or chemotherapy treatment. A significant association between cytokeratin and neuron specific enolase (NSE) expression was demonstrated. Our study supports evidence of epithelial differentiation in ES/PNET and emphasizes that the expression of cytokeratin does not exclude ES/PNET in the differential diagnosis of small round cell tumours.

Implications of continued upregulation of p16INK4a evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix

On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB, releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16 INK4a, a tumour suppressor protein, increases in refl ex response to counter this. 29 histologically re-confi rmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16INK4a expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affi rm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16INK4a, in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were signifi cantly older by about 14-years compared with HSIL (p<0.05) while there was no signifi cant age difference between HSIL and LSIL. p16INK4a expression was signifi cantly increased (p<0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these fi ndings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non-invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC

An analysis of predictive biomarkers in routine histopathological reporting of infi ltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development

Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profi les of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplifi cation by FISH, a small but certain percentage of patients would miss the benefi t of anti-cerbB- 2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to signifi cant ramifi cations on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.

Association of Ki67 with raised transaminases in hepatocellular carcinoma

Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.

Ozonoterapia en SIDA / Ozone therapy in AIDS

Se estudió un paciente SIDA IIIc con fatiga, síndrome de mala absorción intestinal, polineuropatía, anemia, con glucosa, creatinina y tiempo de protombina elevados, conteo CD4 en 37 células carga viral en 2 400 000/mL, el cual venía recibiendo un cóctel de triple terapia retroviral, anemia de 10 g/L. Se le administró un ciclo de ozono por vía rectal, a dosis de 5 mg, junto con interferón, factor de transferencia y eritropoyetina recombinante. Al término del tratamiento se le realizó una evaluación final donde se encontró que desaparecieron la fatiga, las diarreas, la deshidratación y la anemia, aumentando 8 kg de peso y se normalizaron los valores de glucosa, creatinina y tiempo de protombina. Después de 3 meses de finalizado el tratamiento con ozono, continuando con la administración ininterrumpida de interferones y una tetraterapia antirretroviral, el conteo CD4 aumentó a 546 con 30 por ciento y la carga viral disminuyó a 1 700/mL. Se valoró el efecto del ozono como inmunomodulador y antimicrobiano potente en pacientes VIH/SIDA