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Reliability of Prognostic and Predictive Factors Evaluated by Needle Core Biopsies of Large Breast Invasive Tumors.

Author(s): Petrau C, Clatot F, Cornic M, Berghian A, Veresezan L, Callonnec F, Baron M, Veyret C, Laberge S, Thery JC, Picquenot JM

Publication: Am J Clin Pathol, 2015, Vol. 144, Page 555-62

PubMed ID: 26386076 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to compare morphology and immunohistochemical staining of case-matched specimens procured from large breast tumors by surgical resection and NVB and to investigate the effects of tumor heterogeneity, tumor size, and inter-observer variability. Case-matched 14-gauge NCB and surgical resection specimens were obtained from 163 patients with invasive breast carcinomas that were greater than 2 cm. NCBs were immediately fixed in formalin for 24 h while surgically-resected specimens were fixed in formalin within 30 min for at least 48 h. Levels of Ki-67, cyclin A, CK5, and EGFR were investigated in surgical resection specimens via a tissue microarray that contained six 0.6 mm spots of each specimen. All other markers in surgical resection specimens, as well as all biopsy specimens, were evaluated using slide-mounted sections. All staining was evaluated by two pathologists, and a third pathologist evaluated any specimens with discordant findings. Major discordance was defined as discordance when it affected treatment such as changes of SBR from I to III, or changes in ER, PR or HER-2 status.

   Summary of Findings:

   Concordance between surgical resection and NCB specimens for ER IHC, EGFR IHC and HER-2 CISH results was very strong (κ=0.98, 0.92 and 0.91, respectively), while concordance for CK5 IHC, PR IHC, histologic type determination, intrinsic subtype determination and HER2- IHC was strong (k = 0.82, 0.79, 0.74, 0.73, and 0.71, respectively). Concordance between surgical resection and NCB specimens was modest for Ki-67 (k = 0.55) and weak for cyclin A, SBR grade, and MAI determi­nations (k = 0.31, 0.29, and 0.24, respectively), with lower MAI and SBR grade and higher cyclin A IHC staining observed among biopsies compared to surgically resected specimens. Major discordance was found for 11 of the 163 specimen pairs (7%). Of the 11 discordant pairs, three were found to be ER negative in the biopsy and ER positive in the surgical specimen, although one surgical specimen was a mixed histologic type.  SBR grade was higher in the resection than the biopsy specimen in five cases, of these the authors attribute the discrepancy to tumor heterogeneity in two cases, reduced sampling of the carcinoma in one case, and disagreement between pathologists in two cases. HER-2 was unamplified in the NCB and amplified in the resection when analyzed by CISH in three cases, of these the authors attribute the discrepancy to intratumoral heterogeneity (i.e., 2 subtypes in one specimen) in two cases, and to regional variation in amplification in the third case. A high level of intratumoral heterogeneity in the surgical resection specimen was associated with lower concordance with the biopsy specimen for histologic type (k = 0.86 versus k = 0.50, p < .01) and PR IHC staining (k = 0.87 vs k = 0.54, p < .01). Importantly, the authors state major discordance was not correlated to tumor size, number of biopsies obtained, or artifacts (crushing or fixation artifacts); but concordance for ER, HER-2 and cyclin A tended to be lower when the tumor was larger than40mm and concordance in ER, PR, SBR grade, MAI, and histologic type tended to decrease in the presence of artifacts. Finally, concordance among pathologists was strong to very strong for ER, PR and HER-2 (using IHC with CISH) status, but was weak to modest for SBR grade, the MAI, or Ki-67 (k = 0.53, 0.44, and 0.38, respectively).

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Tissue microarray
   DNA	In situ hybridization
   Morphology	H-and-E microscopy
   Protein	Immunohistochemistry

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Acquisition	Method of tissue acquisition	Surgical resection Core needle biopsy
   Preaquisition	Prognostic factor	20-29 mm tumor 30-39 mm tumor >40 mm tumor
   In situ hybridization Specific	Targeted nucleic acid	HER-2
   Immunohistochemistry Specific	Targeted peptide/protein	ER HER-2 PR EGFR ki-67 CK-5
   Immunohistochemistry Specific	Technology platform	CISH
   Biospecimen Aliquots and Components	Biospecimen heterogeneity	Intratumoral sampling (exact positions not specified)

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