• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2021-2023
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• 2012

Purpose: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. Methods: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. Results: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. Conclusion: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10277-10280
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• 2015

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

• Korean Journal of Radiology
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• v.22 no.3
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• pp.464-475
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• 2021

Objective: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification. Materials and Methods: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed. Results: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma. Conclusion: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1973-1978
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• 2016

Background: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. Materials and Methods: Formalin-fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. Results. Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). Conclusions. The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.

• Genomics & Informatics
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• v.18 no.4
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• pp.35.1-35.7
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• 2020

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.459-462
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• 2012

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2 +), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, ${\chi}^2$). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, ${\chi}^2$). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, ${\chi}^2$). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

• Journal of Interdisciplinary Genomics
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• v.2 no.2
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• pp.20-25
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• 2020

Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) is a multisystem lysosomal storage disease that is inherited in an autosomal recessive manner. It consists of four subtypes (MPS IIIA, B, C, and D), each characterized by the deficiency of different enzymes that catalyze the metabolism of the glycosaminoglycan heparan sulfate at the lysosomal level. The typical clinical manifestation of MPS III includes progressive central nervous system (CNS) degeneration with accompanying systemic manifestations. Disease onset is typically before the age of ten years and death usually occurs in the second or third decade due to neurological regression or respiratory tract infections. However, there is currently no treatment for CNS symptoms in patients with MPS III. Invasive and non-invasive techniques that allow drugs to pass through the blood brain barrier and reach the CNS are being tested and have proven effective. In addition, the application of genistein treatment as a substrate reduction therapy is in progress.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1187-1192
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• 2014

Background: To correlate breast cancer subtypes with prognostic factors, microvessel density (MVD), vascular endothelial growth factor (VEGF) expression and clinical features. Materials and Methods: One hundred cases of primary breast carcinoma were classified using biomarkers on tissue microarray as: luminal A [estrogen receptor (ER)+, HER2-, $Ki-67{\leq}14%$], luminal B [ER+, HER2+ or ER+, HER2-, Ki-67>14%], HER2, triple negative basal-like (TNB) [any basal cytokeratins (CKs, 5, 14, 17) and/or endothelial growth factor receptor (EGFR) expression], and TN without such markers [TNN, null], and assessed for p53, vimentin, VEGF and CD31 immunoperoxidase. Results: Of the 100 cases (mean age, 51 years; mean tumor size, 3.2cm; 56% with nodal metastasis; 89 invasive ductal carcinomas, not otherwise specified, 4 invasive lobular carcinomas, 3 metaplastic carcinomas, and 4 other types) there were 39 luminal A, 18 luminal B, 18 HER2, 15 TNB and 10 TNN. The positivities of basal-like markers in the basal-like subtype were 78.3% for CK5, 40% for CK14, 20% for CK17, 46.7% for EGFR. There was no significant difference in age distribution, tumor size, degree of tubular formation, pleomorphism, lymphovascular invasion, nodal metastasis, MVD, VEGF expression and survival among subgroups. TNs demonstrated significantly higher tumor grade, mitotic count, Ki-67 index, p53 and vimentin and decreased overall survival compared with nonTN. Conclusions: The distribution of breast cancer subtypes in this study was similar to other Asian countries with a high prevalence of TN. The high grade character of TN was confirmed and CK5 expression was found to be common in our basal-like subtype. No significant elevation of MVD or VEGF expression was apparent.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8441-8445
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• 2014

Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). Methods: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). Results: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). Conclusion: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

• Korean Journal of Radiology
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• v.23 no.1
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• pp.112-123
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• 2022

Objective: To investigate the relationship between ¹⁸F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations. Materials and Methods: This retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years; age range, 23.0-84.0 years) who had undergone surgical removal of stage IA-IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semi-quantitative parameters were compared between the tumor subtypes using the Mann-Whitney U test or the Kruskal-Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman's correlation. Statistical significance was set at p < 0.05. Results: SUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status. Conclusion: As noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.