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Novel image analysis approach quantifies morphological characteristics of 3D breast culture acini with varying metastatic potentials.

McKeen Polizzotti L, Oztan B, Bjornsson CS, Shubert KR, Yener B, Plopper GE - J. Biomed. Biotechnol. (2012)

Bottom Line: Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades.We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints.These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.

ABSTRACT
Prognosis of breast cancer is primarily predicted by the histological grading of the tumor, where pathologists manually evaluate microscopic characteristics of the tissue. This labor intensive process suffers from intra- and inter-observer variations; thus, computer-aided systems that accomplish this assessment automatically are in high demand. We address this by developing an image analysis framework for the automated grading of breast cancer in in vitro three-dimensional breast epithelial acini through the characterization of acinar structure morphology. A set of statistically significant features for the characterization of acini morphology are exploited for the automated grading of six (MCF10 series) cell line cultures mimicking three grades of breast cancer along the metastatic cascade. In addition to capturing both expected and visually differentiable changes, we quantify subtle differences that pose a challenge to assess through microscopic inspection. Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades. We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints. These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.

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Related in: MedlinePlus

MCF10 series cell lines exhibit variation in acinar structure morphology along the metastatic cascade after 14 days in 3D laminin rich environment culture systems. Cells were cultured in 3D Matrigel suspensions and stained with integrin α3 (red), integrin α6 (green), and DAPI (blue). Example image slices from the six cell lines are typical of those captured during the course of the experiments and are displayed from (a) to (f) as follows: 10A, AT, KCL, DCIS, CA1H, and CA1A.
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fig3: MCF10 series cell lines exhibit variation in acinar structure morphology along the metastatic cascade after 14 days in 3D laminin rich environment culture systems. Cells were cultured in 3D Matrigel suspensions and stained with integrin α3 (red), integrin α6 (green), and DAPI (blue). Example image slices from the six cell lines are typical of those captured during the course of the experiments and are displayed from (a) to (f) as follows: 10A, AT, KCL, DCIS, CA1H, and CA1A.

Mentions: Visual investigation of the acinar structures shown in Figure 1 reveals differences in acini morphology and localization of integrin subunits that are highlighted in Figure 2. Acinar structures in nonmalignant cell lines are comprised of polarized cells that are layered around the hollow lumen that closely approximate the acini formations in mammary glands and lobules. On the other hand, the acinar structures in the tumorigenic cell lines consist of nonpolarized cells that form clusters of cells rather than explicit acini. As shown in Figures 3(a) and 3(b), nontumorigenic cell line 10A and precancerous cell line AT, respectively, exhibit polarized acinar structures that are characterized by the integrin α6 localization at the basal membrane of the cells, integrin α3 localization along the lateral cell membranes, and clear hollow lumen formations. Acinar structures in KCL and DCIS cell lines shown in Figures 3(c) and 3(d), respectively, exhibit significant changes in the integrin subunit densities and their colocalizations. While the basal and lateral membrane protein densities decrease, relative colocalizations of these proteins increase within the acinus. The acinar structures from the noninvasive carcinoma cell lines and acinar-like structures from the invasive carcinoma cell lines CA1H and CA1A shown in Figures 3(e) and 3(f), respectively, are more elongated and exhibit smaller hollow lumens than the acinar structures from the nonmalignant cell lines.


Novel image analysis approach quantifies morphological characteristics of 3D breast culture acini with varying metastatic potentials.

McKeen Polizzotti L, Oztan B, Bjornsson CS, Shubert KR, Yener B, Plopper GE - J. Biomed. Biotechnol. (2012)

MCF10 series cell lines exhibit variation in acinar structure morphology along the metastatic cascade after 14 days in 3D laminin rich environment culture systems. Cells were cultured in 3D Matrigel suspensions and stained with integrin α3 (red), integrin α6 (green), and DAPI (blue). Example image slices from the six cell lines are typical of those captured during the course of the experiments and are displayed from (a) to (f) as follows: 10A, AT, KCL, DCIS, CA1H, and CA1A.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3362088&req=5

fig3: MCF10 series cell lines exhibit variation in acinar structure morphology along the metastatic cascade after 14 days in 3D laminin rich environment culture systems. Cells were cultured in 3D Matrigel suspensions and stained with integrin α3 (red), integrin α6 (green), and DAPI (blue). Example image slices from the six cell lines are typical of those captured during the course of the experiments and are displayed from (a) to (f) as follows: 10A, AT, KCL, DCIS, CA1H, and CA1A.
Mentions: Visual investigation of the acinar structures shown in Figure 1 reveals differences in acini morphology and localization of integrin subunits that are highlighted in Figure 2. Acinar structures in nonmalignant cell lines are comprised of polarized cells that are layered around the hollow lumen that closely approximate the acini formations in mammary glands and lobules. On the other hand, the acinar structures in the tumorigenic cell lines consist of nonpolarized cells that form clusters of cells rather than explicit acini. As shown in Figures 3(a) and 3(b), nontumorigenic cell line 10A and precancerous cell line AT, respectively, exhibit polarized acinar structures that are characterized by the integrin α6 localization at the basal membrane of the cells, integrin α3 localization along the lateral cell membranes, and clear hollow lumen formations. Acinar structures in KCL and DCIS cell lines shown in Figures 3(c) and 3(d), respectively, exhibit significant changes in the integrin subunit densities and their colocalizations. While the basal and lateral membrane protein densities decrease, relative colocalizations of these proteins increase within the acinus. The acinar structures from the noninvasive carcinoma cell lines and acinar-like structures from the invasive carcinoma cell lines CA1H and CA1A shown in Figures 3(e) and 3(f), respectively, are more elongated and exhibit smaller hollow lumens than the acinar structures from the nonmalignant cell lines.

Bottom Line: Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades.We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints.These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.

ABSTRACT
Prognosis of breast cancer is primarily predicted by the histological grading of the tumor, where pathologists manually evaluate microscopic characteristics of the tissue. This labor intensive process suffers from intra- and inter-observer variations; thus, computer-aided systems that accomplish this assessment automatically are in high demand. We address this by developing an image analysis framework for the automated grading of breast cancer in in vitro three-dimensional breast epithelial acini through the characterization of acinar structure morphology. A set of statistically significant features for the characterization of acini morphology are exploited for the automated grading of six (MCF10 series) cell line cultures mimicking three grades of breast cancer along the metastatic cascade. In addition to capturing both expected and visually differentiable changes, we quantify subtle differences that pose a challenge to assess through microscopic inspection. Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades. We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints. These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade.

Show MeSH
Related in: MedlinePlus