1.Cytokeratin immunoreactivity in Ewing sarcoma/ primitive neuroectodermal tumour.
Elbashier, Sha ; Nazarina, Ar ; Looi, Lm
The Malaysian Journal of Pathology 2013;35(2):139-45
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.
2.Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia
Cheah PL ; Koh CC ; Nazarina AR ; Teoh KH ; Looi LM
The Malaysian Journal of Pathology 2016;38(1):33-38
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.
3.Association of Ki67 with raised transaminases in hepatocellular carcinoma.
Phaik-Leng Cheah ; Lai-Meng Looi ; Abdul Rahman Nazarina ; Kein-Seong Mun ; Khean-Lee Goh
The Malaysian journal of pathology 2008;30(2):103-7
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.
Aspartate aminotransferase assay
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Alanine aminotransferase measurement
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Primary carcinoma of the liver cells
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prognostic
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Excision
4.Implications of continued upregulation of p16INK4a evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix
Phaik-Leng CHEAH ; Lai-Meng LOOI ; Kein-Seong MUN ; NAZARINA ; Kean-Hooi TEOH
The Malaysian Journal of Pathology 2011;33(2):83-87
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
5.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
Kean-Hooi TEOH ; Lai-Meng LOOI ; Subathra SABARATNAM ; Phaik-Leng CHEAH ; Abdul Rahman NAZARINA ; Kein-Seong MUN
The Malaysian Journal of Pathology 2011;33(1):35-42
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.
6.Sandstorm Appearance of Pulmonary Alveolar Microlithiasis Incidentally Detected in a Young, Asymptomatic Male.
Li Shyan CH'NG ; Shaik Ismail BUX ; Chong Kin LIAM ; Nazarina Abdul RAHMAN ; Choon Yan HO
Korean Journal of Radiology 2013;14(5):859-862
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.
Biopsy
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Calcinosis/*diagnosis/surgery
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Chronic Disease
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Genetic Diseases, Inborn/*diagnosis/surgery
;
Humans
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*Incidental Findings
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Lung Diseases/*diagnosis/surgery
;
Male
;
Pulmonary Alveoli/pathology/radiography
;
Thoracic Surgery, Video-Assisted/methods
;
Tomography, X-Ray Computed/*methods
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Young Adult