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Aldehyde dehydrogenase 1 expression in primary and metastatic renal cell carcinoma: an immunohistochemistry study.

Abourbih S, Sircar K, Tanguay S, Kassouf W, Aprikian A, Mansure J, Brimo F - World J Surg Oncol (2013)

Bottom Line: ALDH1 expression did not vary significantly based on tumor stage (P = 0.6274) or grade (P = 0.1666).ALDH1 showed significantly more membranous expression in clear cell RCC versus other subtypes (P < 0.0001), as well as in the primary setting compared to metastases (P = 0.0216).The clinical significance of decreased ALDH1 expression in the high stage and metastatic setting remains to be determined in further investigations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, McGill University Health Center, Montreal, QC, Canada. fadi.brimo@muhc.mcgill.ca.

ABSTRACT

Background: ALDH1 has been shown to be a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. We aimed to evaluate the expression of ALDH1 in a cohort of primary and metastatic RCC specimens, and to correlate expression with pathological outcomes such as tumor stage and grade, and clinical outcomes such as progression free survival.

Methods: Three tissue microarrays were constructed from 244 RCC specimens, taken from 1985 to 2006. Samples were stained using an ALDH1 monoclonal antibody and expression was quantified by degree of staining. Membrane and cytoplasm staining were considered separately. A retrospective chart review enabled correlation with clinical outcomes.

Results: ALDH1 expression did not vary significantly based on tumor stage (P = 0.6274) or grade (P = 0.1666). ALDH1 showed significantly more membranous expression in clear cell RCC versus other subtypes (P < 0.0001), as well as in the primary setting compared to metastases (P = 0.0216). In terms of progression free survival, no significant differences were seen based on ALDH1 expression levels. In a subanalysis of clear cell tumors, ALDH1 membranous expression was decreased in tumors of higher stage (P = 0.0233).

Conclusions: ALDH1 may be useful in characterizing RCC tumors as clear cell subtype. However, unlike in other malignancies, ALDH1 may not be useful in prognosticating renal cancers. The clinical significance of decreased ALDH1 expression in the high stage and metastatic setting remains to be determined in further investigations.

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Related in: MedlinePlus

Representative example of staining intensity (a) Staining intensity 0 (no staining); (b) Staining intensity 1 (weak); (c) Staining intensity 2 (moderate); (d) Staining intensity 3 (strong).
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Figure 1: Representative example of staining intensity (a) Staining intensity 0 (no staining); (b) Staining intensity 1 (weak); (c) Staining intensity 2 (moderate); (d) Staining intensity 3 (strong).

Mentions: We purchased mouse anti-human aldehyde dehydrogenase (ALDH1) monoclonal antibody from BD biosciences (Franklin Lakes, NJ, USA). Representative sections were cut from each TMA. Immunohistochemistry was performed using the Ventana automated system and VentanaIview DAB detection kit (Ventana Medical Systems Inc., Tucson, AZ, USA) at the immunohistochemistry laboratory of McGill University Health Center (Montreal, QC, Canada). Optimal dilution was determined by using serial dilutions. The stains were read by one resident (SA), and reviewed by one genitourinary pathologist (FB). Each core was graded according to the intensity of antibody staining (0 = no staining, 1 = minimal staining, 2 = moderate staining, 3 = intense staining). Figure 1 shows examples of each of the staining intensities. We multiplied the proportion of cells that stained in the core with their corresponding staining intensity, then summated for the total H score (maximum 300). If two cores were available from the same specimen then the average H score was used. We reported membrane and cytoplasmic staining separately. Analysis was carried out by a biostatistician using the SAS 9.2 software package (SAS Institute Inc., Cary, NC, USA). For all analyses, a P value less than 0.05 was considered to be statistically significant. Unless otherwise indicated, the Wilcoxon two sample test was employed.


Aldehyde dehydrogenase 1 expression in primary and metastatic renal cell carcinoma: an immunohistochemistry study.

Abourbih S, Sircar K, Tanguay S, Kassouf W, Aprikian A, Mansure J, Brimo F - World J Surg Oncol (2013)

Representative example of staining intensity (a) Staining intensity 0 (no staining); (b) Staining intensity 1 (weak); (c) Staining intensity 2 (moderate); (d) Staining intensity 3 (strong).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842840&req=5

Figure 1: Representative example of staining intensity (a) Staining intensity 0 (no staining); (b) Staining intensity 1 (weak); (c) Staining intensity 2 (moderate); (d) Staining intensity 3 (strong).
Mentions: We purchased mouse anti-human aldehyde dehydrogenase (ALDH1) monoclonal antibody from BD biosciences (Franklin Lakes, NJ, USA). Representative sections were cut from each TMA. Immunohistochemistry was performed using the Ventana automated system and VentanaIview DAB detection kit (Ventana Medical Systems Inc., Tucson, AZ, USA) at the immunohistochemistry laboratory of McGill University Health Center (Montreal, QC, Canada). Optimal dilution was determined by using serial dilutions. The stains were read by one resident (SA), and reviewed by one genitourinary pathologist (FB). Each core was graded according to the intensity of antibody staining (0 = no staining, 1 = minimal staining, 2 = moderate staining, 3 = intense staining). Figure 1 shows examples of each of the staining intensities. We multiplied the proportion of cells that stained in the core with their corresponding staining intensity, then summated for the total H score (maximum 300). If two cores were available from the same specimen then the average H score was used. We reported membrane and cytoplasmic staining separately. Analysis was carried out by a biostatistician using the SAS 9.2 software package (SAS Institute Inc., Cary, NC, USA). For all analyses, a P value less than 0.05 was considered to be statistically significant. Unless otherwise indicated, the Wilcoxon two sample test was employed.

Bottom Line: ALDH1 expression did not vary significantly based on tumor stage (P = 0.6274) or grade (P = 0.1666).ALDH1 showed significantly more membranous expression in clear cell RCC versus other subtypes (P < 0.0001), as well as in the primary setting compared to metastases (P = 0.0216).The clinical significance of decreased ALDH1 expression in the high stage and metastatic setting remains to be determined in further investigations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, McGill University Health Center, Montreal, QC, Canada. fadi.brimo@muhc.mcgill.ca.

ABSTRACT

Background: ALDH1 has been shown to be a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. We aimed to evaluate the expression of ALDH1 in a cohort of primary and metastatic RCC specimens, and to correlate expression with pathological outcomes such as tumor stage and grade, and clinical outcomes such as progression free survival.

Methods: Three tissue microarrays were constructed from 244 RCC specimens, taken from 1985 to 2006. Samples were stained using an ALDH1 monoclonal antibody and expression was quantified by degree of staining. Membrane and cytoplasm staining were considered separately. A retrospective chart review enabled correlation with clinical outcomes.

Results: ALDH1 expression did not vary significantly based on tumor stage (P = 0.6274) or grade (P = 0.1666). ALDH1 showed significantly more membranous expression in clear cell RCC versus other subtypes (P < 0.0001), as well as in the primary setting compared to metastases (P = 0.0216). In terms of progression free survival, no significant differences were seen based on ALDH1 expression levels. In a subanalysis of clear cell tumors, ALDH1 membranous expression was decreased in tumors of higher stage (P = 0.0233).

Conclusions: ALDH1 may be useful in characterizing RCC tumors as clear cell subtype. However, unlike in other malignancies, ALDH1 may not be useful in prognosticating renal cancers. The clinical significance of decreased ALDH1 expression in the high stage and metastatic setting remains to be determined in further investigations.

Show MeSH
Related in: MedlinePlus