Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias

Bratthauer, Gary L.; Moinfar, Farid; Stamatakos, Michael D.; Mezzetti, Thomas; Shekitka, Kris M.; Man, Yan‐gao; Tavassoli, Fattaneh A.

doi:10.1053/hupa.2002.124789

Cited by 123 publications

(77 citation statements)

References 19 publications

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“…A previous study reported high molecular weight keratin 34bE12, which is reactive against cytokeratins 1, 5, 10, and 14, to be a useful marker in differentiating DCIS from LCIS. 17 However, another study has shown it to not be a specific marker for lobular differentiation. 18 Our data supports the latter conclusion, although few cases of each were included in the present study.…”

Section: Discussionmentioning

confidence: 99%

The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study

2007

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Tubulolobular carcinoma is a type of mammary carcinoma that displays an admixture of invasive tubules and lobular-like cells. Previous reports have shown it to share clinical similarities to lobular carcinoma, whereas more recent studies have shown it to be E-cadherin positive. The aim of the current study was to further explore the immunophenotype of tubulolobular carcinoma, and to document its natural behavior. Nineteen cases of tubulolobular carcinoma and 10 cases each of tubular and lobular carcinoma were retrieved for comparison analysis. Immunohistochemistry was performed with antibodies against estrogen receptor, progesterone receptor, HER2/neu, 34bE12, E-cadherin, and the catenins. Twenty-five percent of patients with tubulolobular carcinoma presented with greater than stage I disease, compared to 0 and 60% of patients with tubular and lobular carcinoma, respectively. Two patients with tubulolobular carcinoma had tumor recurrence, one of whom also developed metastasis. The majority of all carcinomas were estrogen and progesterone receptor positive. Ecadherin displayed membranous staining in all tubular and tubulolobular carcinomas, and was negative in all lobular carcinomas. Half of each carcinoma subtype displayed granular cytoplasmic 34bE12 immunoreactivity. a-Catenin exhibited partial or complete membranous staining in all tubulolobular and tubular carcinomas, and was negative in all lobular carcinomas. b-Catenin displayed membranous staining in tubulolobular and tubular carcinomas, whereas all lobular carcinomas had coarse cytoplasmic immunoreactivity. p120 and c-catenin displayed membranous staining in 100% of tubulolobular and tubular carcinomas and cytoplasmic staining in 100% of lobular carcinomas. Tubulolobular carcinoma of the breast is thus a distinct type of mammary carcinoma that displays both tubular and lobular patterns histologically but displays the membranous Ecadherin/catenin complex characteristic of the ductal immunophenotype. Tubulolobular carcinoma appears to be more aggressive than tubular carcinoma, as 16% of patients had lymph node metastases, although all were alive at a mean follow-up of 40 months. The distinction between ductal and lobular carcinomas of the breast can usually be made by applying typical cytologic and architectural criteria, such as tubule formation and pleomorphism in the former, and dyscohesion of tumor cells in the latter. However, some carcinomas display overlapping features, making this distinction difficult. Tubulolobular carcinoma is a distinct type of mammary carcinoma that, as its name suggests, displays an admixture of minimally pleomorphic invasive tubules, as seen in classic tubular carcinoma, and dyscohesive cells with low-nuclear grade, as seen in classic lobular carcinoma. As tubulolobular carcinomas are rare neoplasms, representing less than 3% of all breast cancers, relatively few studies aimed at their analysis have been performed, and thus little is known about their behavior. A study published in 1977 by Fisher et al 1 concluded that these ...

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Section: Discussionmentioning

confidence: 99%

The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study

2007

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“…Available worldwide and in use for 20 years, clone 34 ␤ E12 is believed to be reactive against keratin proteins 1, 5, 10, and 14, according to the manufacturer (Gown and Vogel 1982). This antibody shows a perinuclear, often polarized immunoreactivity in every LIN we have evaluated, 40 of which have been reported on (Bratthauer et al 2002) and in an additional 20 cases studied since.This study was designed to determine which of the four keratin proteins identified by 34 ␤ E12 were detected in the cells of LIN.To that end, we tested individual antibodies reactive against keratins 1, 5, 10, and 14 on classic LIN. To our surprise, none of these reacted with the cells of LIN.…”

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confidence: 99%

“…L obular intraepithelial neoplasia (LIN) is a disease of the breast that increases the risk for breast cancer in those afflicted (Tavassoli 1999). LIN cells are usually characterized by a lack of E-cadherin protein along with the presence of a high molecular weight cytokeratin as demonstrated by immunohistochemistry (IHC) with the commonly used antibody clone 34 ␤ E12 (Bratthauer et al 2002). Available worldwide and in use for 20 years, clone 34 ␤ E12 is believed to be reactive against keratin proteins 1, 5, 10, and 14, according to the manufacturer (Gown and Vogel 1982).…”

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confidence: 99%

Cytokeratin Immunoreactivity in Lobular Intraepithelial Neoplasia

Bratthauer

Miettinen

Tavassoli³

2003

J Histochem Cytochem.

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S U M M A R Y Eighteen commercially available antibodies reactive against different cytokeratin proteins were tested on classic examples of lobular intraepithelial neoplasia (LIN) and of ductal intraepithelial neoplasia (DIN) of the breast. About 90% of higher-grade DIN (AIDH and DCIS) show no or substantially diminished reaction with clone 34 ␤ E12 (specified as reactive against keratins 1, 5, 10, and 14 as determined by the manufacturer), while the cells of LIN were found to express the antigen reactive with this antibody. To determine which of these four keratins are present in the cells of LIN, antibodies reactive against these individual four keratins were tested. None of the four antibodies to keratins 1, 5, 10, or 14 reacted with the cells of LIN. To investigate this further, 13 additional monoclonal antibodies to various other keratin proteins were tested on the cells of LIN. Those that successfully reacted with the cells of LIN were further tested on the cells of DIN. All of the individual antibodies reactive with the cells of LIN were also reactive with the cells of DIN to a degree, with clone RCK108 (reactive against keratin 19) coming the closest to demonstrating the reactivity seen with 34 ␤ E12. We conclude that the reactivity seen in the cells of LIN with 34 ␤ E12 is due to either (a) a crossreaction with keratin 19 that is slightly less prominent than the reaction of the individual clone RCK108, (b) a crossreaction with a keratin protein that was not tested (3, 11, 12), (c) a crossreaction with a protein closely resembling keratin in formalin-fixed, paraffin-embedded tissue, or (d) the detection of a mutated or truncated form of keratin 1, 5, 10, or 14 that cannot be detected by the individual monoclonal antibody. L obular intraepithelial neoplasia (LIN) is a disease of the breast that increases the risk for breast cancer in those afflicted (Tavassoli 1999). LIN cells are usually characterized by a lack of E-cadherin protein along with the presence of a high molecular weight cytokeratin as demonstrated by immunohistochemistry (IHC) with the commonly used antibody clone 34 ␤ E12 (Bratthauer et al. 2002). Available worldwide and in use for 20 years, clone 34 ␤ E12 is believed to be reactive against keratin proteins 1, 5, 10, and 14, according to the manufacturer (Gown and Vogel 1982). This antibody shows a perinuclear, often polarized immunoreactivity in every LIN we have evaluated, 40 of which have been reported on (Bratthauer et al. 2002) and in an additional 20 cases studied since.This study was designed to determine which of the four keratin proteins identified by 34 ␤ E12 were detected in the cells of LIN.To that end, we tested individual antibodies reactive against keratins 1, 5, 10, and 14 on classic LIN. To our surprise, none of these reacted with the cells of LIN. We then obtained monoclonal antibodies (MAbs) to an additional 13 keratin proteins to determine if there was a previously unrecognized or undetected crossreaction of 34 ␤ E12 with another keratin protein in formalin-fixed, paraff...

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“…CK 8 37 and high molecular weight cytokeratin 17,55,56 have been used to distinguish between duct and lobular lesions, but we were not able to reproduce the same results. We are in the process of testing other immunomarkers such as catenins and other cadherin antibodies to distinguish lobular neoplasia or duct neoplasia.…”

Section: (10%)mentioning

confidence: 38%

Interobserver variability and aberrant E-cadherin immunostaining of lobular neoplasia and infiltrating lobular carcinoma

et al. 2008

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The distinction between lobular neoplasia and infiltrating lobular carcinoma from ductal neoplasia and infiltrating duct carcinoma with equivocal histologic features may present a challenge as this distinction has important therapeutic implications. Although E-cadherin staining has been of value in helping to make this determination, the variability of the E-cadherin staining pattern and the immunohistochemistry techniques can be problematic in clinical practice. A total of 161 cases of breast lesions previously diagnosed as lobular neoplasia and infiltrating lobular carcinoma were selected from the departmental files. Three surgical pathologists interpreted them in a blinded manner for the histology diagnoses and E-cadherin staining. E-cadherin staining was conducted on the paraffin-embedded sections of the breast lesions using two different source antibodies. Our results using morphology and E-cadherin stain agreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 140 of 161 cases (86.9%). Among the 140 cases, three pathologists agreed with the morphologic diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 100 (71.4%), two pathologists in 26 (18.6%) and one pathologist in 14 (10%). All three pathologists disagreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma but reevaluated as ductal lesions in 21 cases (13.0%). E-cadherin staining was confirmatory in 136 of total 161 cases (84.5%) of both lobular and duct lesions by showing the loss of staining in lobular lesions and the presence of complete membrane staining in duct lesions. Aberrant E-cadherin reactions were retained weak or partial incomplete thin membrane reaction in lobular-type lesions and reduced membrane reaction in ductal-type lesions were seen in 25 of the total 161 cases (15.5%). E-cadherin immunoreaction with two different antibodies showed discrepant results in 5 of 78 cases tested (6.4%). This study illustrates (1) interobserver variability of the morphologic diagnoses of lobular neoplasia/infiltrating lobular carcinoma and duct neoplasia/infiltrating duct carcinoma, (2) the occasional presence of aberrant E-cadherin stain pattern in these breast lesions and (3) variability of E-cadherin immunostaining results by two different antibodies.

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Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias

Cited by 123 publications

References 19 publications

The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study

The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast: an immunohistochemical and clinicopathologic study

Cytokeratin Immunoreactivity in Lobular Intraepithelial Neoplasia

Interobserver variability and aberrant E-cadherin immunostaining of lobular neoplasia and infiltrating lobular carcinoma

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