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What is Ki-67?

It is a test that measures the rate of proliferation of malignant cells.  Tumors with a rate equal to or less than 14% have slow growth and, equal to or above 30%, represent a high growth rate.

Immunohistochemical analysis may include other tests, such as androgen receptor, DNA repair proteins, oncogenes, etc.

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How is breast cancer molecular classification?

Through the analysis of estrogen receptor, progesterone receptor, oncoprotein HER2 / c-erbB-2 and Ki-67 antigen markers it is possible to define one of the four molecular profiles of breast carcinoma:  Luminal A, Luminal B, HER2 or Basal/Triple negative. This definition has a predictive value, as it helps to choose the most appropriate treatment.

These tumor subgroups show similarities and differences, both in gene expression, growth rate, signaling pathways, cell composition, prognosis and sensitivity to therapy.

Lamp A

It is a tumoral form originating from differentiated epithelial cells of the ducto-lobular lumens, typically with the presence of ER (estrogen receptor) and RP (progesterone receptor) in large numbers of cells, and absence of HER-2. It corresponds to about 30 to 40% of cases. The Ki 67 evaluation shows a low proliferation rate (<14%). These tumors are very sensitive to hormone therapy.

Lamp B

They also originate in ER-rich luminal epithelial cells. RP, on the other hand, can be present in both a high and a low proportion of cells. The HER-2 oncogene protein can be detected and the proliferation rate assessed by Ki 67 is higher (>14%). This tumor is also sensitive to hormone therapy and Trastuzumab can be used successfully if it is HER-2 positive. Luminal subtype B corresponds to about 20 to 30% of breast carcinomas.

HER-2 superexpressor

On average, 15 to 20% of cases are of this subtype. The HER-2 oncogene is overexpressed by gene amplification. In its natural evolution, it is classically associated with a poor prognosis, a scenario that was changed with the introduction of targeted anti-HER-2 therapy, by Trastuzumab or Pertuzumab combined with chemotherapy. Most of these tumors are ER negative.

basaloid

It is also estimated that 15 to 20% of breast carcinomas are basaloid. They are poorly differentiated or undifferentiated lesions (generally GIII), with a high proliferation rate. Most (80%) are triple-negative tumors by immunohistochemical reaction, with ER, RP and HER-2 negativity; however, the terms basaloid and triple-negative are definitely not synonymous: the first is defined by gene expression in a DNA microarray, and the second, by immunohistochemical criteria. The proposed bookmark panel. for the classification of the basal type, it would be the absence of expression of ER, RP and HER2, expression of high molecular weight/basal cytokeratins, CK5/6, 14 or 17, and expression of EGFR (HER-1).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                                         Molecular classification of breast cancer

What is liquid biopsy?

The name “liquid” comes from the technique: the collection, in this case, is bodily fluids, including saliva, urine and cerebrospinal fluid (cerebrospinal fluid), but mainly blood. .Innovative procedure, the liquid biopsy has this name because it performs, in some circumstances, a function similar to a traditional biopsy: to define molecular characteristics of the cancer and monitor its evolution,  but with the benefit of not submitting the patient to an invasive procedure, as in traditional biopsies, which consist in removing part of the tumor for subsequent laboratory analysis.

However, in reality, with the traditional biopsy, one seeks to receive a report to discover the existence of a cancer cell in the region, and with the liquid, one discovers the types of genetic mutations that are present in cancer cells.

What are its benefits?

Blood testing is possible because tumors leave "trails" in the bloodstream, such as circulating tumor cells (CTCs), circulating tumor DNA fractions (ctDNA) and other microscopic structures that help doctors understand the subtype and characteristics of cancer.

ctDNA levels vary according to several factors, such as type of cancer, tumor location, vascularity and cell turnover. According to a recent study, most stage 3 and 4 (also known as metastatic) patients of liver, ovarian, colon, stomach, breast, esophagus, pancreas, bladder and head and neck cancers and melanoma have detectable ctDNA levels .

In addition to assisting in the genotyping (gene analysis) of solid cancers in a minimally invasive way, liquid biopsy also allows tracking the progression or shrinkage of the tumor, tracing its molecular profile, and helps to discover the imminence of resistance, for sure medicine. Thus, monitoring the patient's condition is much more effective.

Liquid biopsy is relevant as it detects mechanisms of primary and acquired resistance to treatments. ctDNA can be exploited to monitor clonal evolution and identify heterogeneous drug resistance mechanisms.

Thus, the procedure allows doctors to monitor whether the cancer is reacting as expected to a therapy, through CTCs. With the circulating tumor DNA fractions, the professional is able to understand which genetic mutations occurred. Therefore, therapy is better targeted, becoming more effective.

In the future, we hope to use liquid biopsy to screen patients and increase early diagnosis.

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Sorocaba Medical Center

Botafogo

Rua Sorocaba, 464 - room 202

Tel. 21 2537-0138 / 2539-5093

    Second fourth  it's Friday

Americas Medical City

Barra da Tijuca

Av. Jorge Curi, 550 - rooms 252/253

Tel. 21 3264-4866 / 3264-4863

    Tuesday and Thursday

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