Semi-automated evaluation of Ki-67 index in invasive ductal carcinoma of the breast

Abstract

A significant factor that affects the value of the Ki-67 proliferation index (IK) is the interpretation and implementation approach. This method is based on visual or automated methods to count tumor nuclei labeled with Ki-67 antigen, and is prone to errors. Detection of Ki-67 is a useful tool in breast cancer and contributes to its molecular classification. The current study proposes a method for the quantification of Ki-67-positive tumor nuclei, which allows for the determination of the exact IK value that is required for tumor stratification based on the proliferation rate. The IK was assessed in 81 successive cases of diagnosed invasive ductal breast carcinoma using a semi-automated method that accurately identifies positive tumor cell nuclei. This method prevents the inclusion of other possible positive cells, including lymphoid, normal epithelia and hyperplastic. In small specimens with increased cell density, where the nucleus/cytoplasm ratio is markedly in favor of the nucleus and the distance between nuclei is small, the method allows precise quantification of the nuclei, even when the limits between nuclei are difficult to identify. In addition, images may be stored in a database, including the assessments, and easily accessed when required. We hypothesize that the semi-automated method for counting nuclei offers the most accurate method of assessing the IK and avoids counting errors that may occur through other methods.

Ki-67 as a prognostic marker according to breast cancer molecular subtype

“…Only nuclear staining (plus mitotic figures stained with Ki-67) should be incorporated into the Ki-67 score that is defined as the percentage of positively stained cells among the total number of malignant cells scored. Similar to other IHC stains, internal positive controls, such as mitotic figures, normal ducts, and lymphocytes, and endothelial and stromal cells (lesser extent), are helpful 11,12 . …”

“…Uncontrolled proliferation is a distinct characteristic of malignancy and may be assessed through various methods, including counting mitotic figures in stained tissue sections, incorporation of labeled nucleotides into DNA, and flow cytometric evaluation of cell fraction in S phase 11 . Dowsett et al 12 reviewed that the most common measurement involves immunohistochemical assessment of Ki-67 antigen.…”

Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?

“…The number of ER, PR, Ki-67 positive cells was evaluated on a Nikon Eclipse 80i instrument using a Nikon DS-Fi1 installed camera and Nis-elements 2.30 imaging software in accordance with Suciu's method [15]. The average from ten microscope fields (40×) with the greatest number of positive cells was determined.…”

Evaluation of Vascular Proliferation in Molecular Subtypes of Breast Cancer

“…Proliferating microvessels were counted in the same fields as MVD, at ×400 magnification and were defined as cells lining the vessel lumen that expressed both CD34 (red staining) and Ki67 (brown staining). Proliferative vessels were counted in a semi-automated manner using the method previously described by Suciu et al (14).…”