Journal of Pathology and Translational Medicine

Original Articles

p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell Carcinoma: Khairunisa Ahmad Affandi, Nur Maya Sabrina Tizen, Muaatamarulain Mustangin, Reena Rahayu MdReena Rahayu Md Zin; J Pathol Transl Med. 2018;52(5):283-289. Published online August 31, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.14

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Background
Lung cancer is the third most common cancer worldwide. With major advances in the molecular testing of lung cancers and the introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma as well as pathologic subtyping has become important. Recent studies showed that p40 is highly specific for squamous and basal cells and is superior to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker.
Methods
Seventy formalin-fixed paraffin-embedded cases previously diagnosed as primary lung squamous cell carcinoma (n = 35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies in lung squamous cell carcinoma and lung adenocarcinoma were compared.
Results
p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell carcinoma was strong and diffuse, whereas variable reactivity was observed in lung adenocarcinoma.
Conclusions
p40 is an excellent marker for distinguishing lung squamous cell carcinoma from adenocarcinoma, and p40 expression is equivalent to p63 expression in lung squamous cell carcinoma.

Citations

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Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small Cell Lung Carcinoma Using a Panel of Bcl-2, p63, and 34betaE12.: Jun Zhe Li, Chan Choi, Yoo Duk Choi, Kook Joo Na; Korean J Pathol. 2011;45(2):170-174.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.170

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Abstract PDF: BACKGROUND
Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors.
METHODS
We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56.
RESULTS
A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC.
CONCLUSIONS
Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.

Expression of p63 and its Isoform, deltaNp63, in Non-Small Cell Lung Carcinoma.: Ick Doo Kim, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Gi Yeong Huh, Mee Young Sol, Min Ki Lee, Young Dae Kim, Chang Hun Lee; Korean J Pathol. 2009;43(4):321-328.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.321

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Abstract PDF: BACKGROUND
Several studies have been conducted on the role of the p63 gene family in non-small cell lung carcinoma (NSCLC). Nevertheless, the role of these genes in the development and progression of NSCLC remains controversial. This study was designed to examine the expression and clinicopathologic significance of the p63 family in NSCLC.
METHODS
Immunohistochemical staining was performed on 92 cases of NSCLC (47 squamous cell carcinomas [SqCCs] and 45 adenocarcinomas [ACs]) using tissue microarray blocks. The results were analyzed and correlated with clinicopathologic data. RESULTS: The expression of delta Np63 (Delta Np63) was elevated in SqCC (39/47), but not in AC (2/45; p<0.01). Both p63 and Delta Np63 had high expression in 39 SqCCs; p63 and Delta Np63 also had a similar geomorphologic distribution in most positive tumors. The expression of Delta Np63 was correlated with histologic type, gender, pT stage, p53 expression, and p63 expression. pT and pN stages were independent factors in survival (p<0.05, respectively).
CONCLUSIONS
The major p63 isoform in NSCLC, Delta Np63, had a strong correlation with p53 and p63, and was exclusively expressed in SqCC. However, our findings suggest that Delta Np63 was not an independent prognostic factor for NSCLC.

Metaplastic Squamous Carcinoma of the Breast: Clinicopathologic Analysis of 17 Cases.: Sun Ah Lee, Kyung Eun Lee, Byung In Moon, Woon Sup Han, Sun Hee Sung; Korean J Pathol. 2009;43(1):20-25.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.20

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Abstract PDF

BACKGROUND
Squamous cell carcinoma of the breast is very rare and it is considered to arise from metaplastic change of ductal carcinoma. Metaplastic squamous cell carcinoma (MSC) of the breast includes pure squamous cell carcinoma, metaplastic adenosquamous carcinoma and low grade adenosquamous carcinoma. Most of the cases of MSC of the breast were reported to have lymph node metastasis and this has a worse prognosis than that of conventional invasive ductal carcinoma.
METHODS
We collected 17 cases of MSC of the breast from 1,173 cases of breast cancer and analyzed the clinicopathological characteristics.
RESULTS
The age range was 31 to 69 years (mean age: 47.2). The mean tumor size was 3.6 cm. Twelve cases (70.6%) had a negative nodal status. The majority of the cases were of a high nuclear grade (grade III: 76.5%), and a high histologic grade (grade III: 88.2%). All the cases had no amplification of HER2, and they were negative for hormonal receptors, except for 2 cases with weak positivity. All the cases showed positivity for EGFR (3+: 14 cases, 1+: 3 cases). Clinical relapse was found in 3 patients on follow up and two of them expired due to lung and bone metastasis.
CONCLUSIONS
MSC is associated with high nuclear and histologic grades, a high EGFR expression and they are triple negative for ER, PR, and HER2. The EGFR immunopositivity of MSC suggests a basal-like subtype.

Citations

Citations to this article as recorded by

Eccrine ductal and acrosyringeal metaplasia in breast carcinomas: report of eight cases
Tibor Tot
Virchows Archiv.2019; 474(3): 383. CrossRef
Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
The Korean Journal of Pathology.2011; 45(1): 53. CrossRef

Expression of p63,bcl-2,bcl-6 and p16 in Basal Cell Carcinoma and Squamous Cell Carcinoma of the Skin.: Zhenlong Zheng, Youngchul Kye, Xianglan Zhang, Aeree Kim, Insun Kim; Korean J Pathol. 2005;39(2):91-98.

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Abstract PDF: BACKGROUND
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the common malignant neoplasms of the skin. The p63 is a p53 homologue which is considered to be a reliable keratinocyte stem cell marker. Bcl-2 plays a key role in cell longevity by preventing apoptosis, whereas the bcl-6 gene functions as a transcriptional repressor. The p16-CDK4/6 complex arrests the cell cycle at G0 /G1 phase. In the present study, the expression of p63, bcl-2, bcl-6, and p16 in BCC and SCC was evaluated.
METHODS
Forty-seven BCCs and 43 SCCs were selected and microarrayed in paraffin blocks. Immunohistochemical analysis was performed with specific antibodies for bcl-2, bcl-6, p16 and p63.
RESULTS
p63 was found to be expressed in all BCCs and SCCs. Bcl-2 was exclusively expressed in BCCs (100%), but there was negative expression in SCCs, whereas bcl-6 was positively expressed in 18.2% of SCCs, and was negative in BCCs. In SCCs, p16 was expressed at high frequency (47.7%) than in BCCs (14.9%). The expression of p16 was correlated with the histologic grades of SCCs.
CONCLUSION
The different patterns of bcl-2, bcl-6, p63 and p16 protein expression between BCCs and SCCs may represent the different histogenesis and morphologic features of two lesions.

Analysis of Expression of p63 in Cervical Neoplasia Comparing with Other Immunohistochemical Markers .: Min Yeong Kim, Sam Hyun Cho, Moon Hyang Park; Korean J Pathol. 2003;37(5):333-341.

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Abstract PDF: BACKGROUND
The reproducibility in grading a cervical intraepithelial neoplasia (CIN) are not perfect. The aim of this study was to assess the value of the immunohistochemical expression of p63 and the other biomarkers for grading a CIN (dysplasia and in situ carcinoma), and diagnosing invasive carcinomas.
METHODS
Sixty six cervical specimens were immunostained with the monoclonal antibodies against p63, Ki-67, p27Kip1, and p53 to determine the localization.
RESULTS
The p63 positive cells are well linked with squamous cell maturation and the degree of dysplasia. In mild dysplasia, the p63 positive cells were localized to the basal and parabasal cells, which gradually extended into the middle and upper layers in moderate and severe dysplasia. p63 expression was strong in immature squamous epithelium and invasive squamous cells, but was constantly absent in an adenocarcinoma. The Ki-67 positive cells were scattered from the parabasal cells to the superficial cells in accordance with the degree of dysplasia. p27Kip1 expression was noted in the intermediate cells in the normal cervix. In CIN, the p27Kip1 positive nuclei tended to extend to the basal cells, but it showed no diagnostic consistency in an invasive carcinoma. p53 expression was also variable.
CONCLUSION
p63 is a useful diagnostic adjunct for grading CIN as well as for detecting microinvasion and squamous differentiation in invasive carcinoma. However, immunohistochemical expressions for the p27Kip1 and p53 have no correlation with the grade of CIN and squamous cell carcinoma.

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