Objective The purpose of this study was to investigate and classify the molecular subtypes of high-grade DCIS and identify possible high-risk subtypes. The heterogenicity of DCIS with variable clinical and histopathological presentations has been recognized. Nevertheless, only histopathological grading and diameter are currently implemented in clinical decision-making following the diagnosis of DCIS. The molecular subtypes of DCIS and their IHC surrogate markers have not been defined in conventional treatment guidelines and recommendations. We applied the definitions of molecular subtypes according to the IHC surrogate markers defined for IBC and subclassified high-grade DCIS, accordingly. Methods The histopathological specimens from 494 patients diagnosed with DCIS between 1996 – 2018, were collected, revised and regraded. Other in situ and papillary lesions of breast were excluded. 357 high-grade DCIS cases were submitted to IHC analysis. The investigated markers were ER, PR, HER2, and Ki-67. Results 45 were classified as grade 1, 19 as grade 2, and 430 as grade 3. 64 patients with high-grade DCIS had an additional invasive component in the surgical specimen. 33 patients were diagnosed with recurrent DCIS or invasive cancer (minimum one year after their primary DCIS diagnosis). The proportions of luminal A and luminal B HER2-negative subtypes varied depending on whether 2011 or 2013 St. Gallen Consensus Conference guidelines were adopted. Luminal A was the most prevalent subtype, according to both classifications. The luminal B HER2-positive subtype was found in 22.1% of cases, HER2-enriched subtype in 21.8%, and TPN subtype in 5.6%. HER2-enriched subtype was significantly more frequent among DCIS with invasive component (p = 0.0169). Conclusions High-grade DCIS exhibits all the molecular subtypes previously identified in IBC, but with a somewhat different distribution in our cohort. HER2-enriched subtype is substantially related to the existence of an invasive component in DCIS; consequently, it is regarded as a high-risk entity.
Background: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group with variable clinical presentation. 70-80% of DCIS are classified as grade 3 (Van Nuys Classification). They are treated according to grade and extension of the lesion, as was the standard treatment for invasive breast cancer in the 1970`s. Molecular genetic studies of invasive breast carcinomas (BC) have defined a molecular subclassification. In routine diagnostics, we use surrogate markers like estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) as tools to stratify for treatment. The individual results of these surrogate markers have resulted in a complex treatment algorithm. In contrast, still all DCIS grade 3 are given the same treatment. Aim: To investigate the molecular subtypes of DCIS diagnosed at the Department of Pathology, Akershus University Hospital (Norway). Materials: 483 histological specimens of DCIS at Akershus University Hospital, Dep. of Pathology, during 1996-2018. All relevant background information was recorded. Methods: All histological sections have been reassessed, and the grading has been confirmed independently by two experienced pathologists. An eventual peritumoral inflammatory component was made note of. All grade 3 DCIS with representative paraffin blocks were submitted for immunohistochemistry (IHC). The investigated markers were ER, PR, Ki-67 and HER-2. Results: The age ranged from 33-90, with a mean and median of 57 years. 10.4% were grade 1, 3.9% as grade 2 and 85.7% as grade 3. The size of DCIS ranged from 0,5 to150 mm, with mean 28 mm and median of 20 mm. 64 patients had an invasive component, 51 of them with a size of <5 mm (pT1a), and 13 > 5 mm but < 10 mm (pT1b). 33 (6,8%) patients were diagnosed with a recurrent DCIS or cancer (minimum 1year after primary DCIS diagnosis). Six patients were deceased (1 was diagnosed with new ipsilateral DCIS 3 years later, 2 with cancer in the contralateral breast, 2 with cancer in ipsilateral breast and 1 with new DCIS in the ipsilateral breast). The preliminary results of immunohistochemical studies of 245 cases indicate: Luminal A: 30.7% (Ki-67 <14%), Luminal B: 42% (Ki-67> 14%) and non-luminal 27.3%. Around 33% of the non-luminal cases are expected to be triple negative. Histomorphologically, we have found peritumoral lymphoid cells in 31% of cases, and all of these (100%) are DCIS grade 3. Conclusions: The molecular subtypes identified in invasive breast carcinomas are all represented in DCIS G3 and further studies might reveal the possibility of a more adapted treatment algorithm, as in invasive BC. The peritumoral inflammatory cell infiltrates will be investigated in future studies. Citation Format: Hossein Schandiz, Daehoon Park, Yan Liu Kaiser, Marianne Lyngra, Ingrid Solvang Talleraas, Jürgen Geisler, Torill Sauer. A novel diagnostics approach to Ductal Carcinoma In Situ (DCIS) with potential impact on the therapeutic algorithms [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A015.
Objective The purpose of this study was to investigate and classify the molecular subtypes of high-grade ductal carcinoma in situ (DCIS) and identify possible high-risk subtypes. The heterogenicity of DCIS with variable clinical and histopathological presentations has been recognized. Nevertheless, only histopathological grading and diameter are currently implemented in clinical decision-making following the diagnosis of DCIS. The molecular subtypes of DCIS and their IHC surrogate markers have not been defined in conventional treatment guidelines and recommendations. We applied the definitions of molecular subtypes according to the IHC surrogate markers defined for IBC and subclassified high-grade DCIS, accordingly. Methods Histopathological specimens were collected, revised, and regraded from 494 patients diagnosed with DCIS between 1996 and 2018. Other in situ and papillary lesions observed in breast biopsies were excluded from this study. 357 high-grade DCIS cases were submitted to IHC analysis. The markers investigated were ER, PR, HER2, and Ki67. Results 45 cases were classified as grade 1, 19 as grade 2, and 430 as grade 3. Sixty patients with high-grade DCIS had an additional invasive component in the surgical specimen. Thirty-three patients were diagnosed with recurrent DCIS or invasive cancer (minimum one year after their primary DCIS diagnosis). The proportions of luminal A and luminal B HER2-negative subtypes varied depending on whether 2011 or 2013 St. Gallen Consensus Conference guidelines were adopted. Luminal A was the most prevalent subtype, according to both classifications. The luminal B HER2-positive subtype was found in 22.1% of cases, HER2-enriched subtype in 21.8%, and TPN subtype in 5.6%. There were strong indications that HER2-enriched subtype was significantly more frequent among DCIS with invasive component (p = 0.0169). Conclusions High-grade DCIS exhibits all the molecular subtypes previously identified in IBC, but with a somewhat different distribution in our cohort. HER2-enriched subtype is substantially related to the presence of an invasive component in DCIS; consequently, it is regarded as a high-risk entity.
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