Biomedical subjects

Takanori Ishida

Publications and source records attributed to Takanori Ishida.

At least 19 recordsLinked to original sources

PubMed2007

5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production.

Previous in vitro studies demonstrated that bioactive androgen 5alpha-dihydrotestosterone (DHT) exerted antiproliferative effects through an interaction with androgen receptor (AR) in breast carcinoma cells. However, AR status has not been examined in association with DHT concentration in breast carcinoma tissues, and significance of androgenic actions remains unclear in breast carcinomas. Therefore, in our study, we first examined intratumoral DHT concentrations in 38 breast carcinoma tissues using liquid chromatography/electrospray tandem mass spectrometry. Intratumoral DHT concentration was positively associated with 5alpha-reductase type 1 (5alphaRed1), and negatively correlated with aromatase. We then examined clinical significance of AR and 5alphaRed1 status in 115 breast carcinoma tissues by immunohistochemistry. Breast carcinomas positive for both AR and 5alphaRed1 were inversely associated with tumor size or Ki-67. These patients showed significant associations with a decreased risk of recurrence and improved prognosis for overall survival, and the AR / 5alphaRed1 status was demonstrated an independent prognostic factor. Moreover, we examined possible regulation of DHT production by aromatase in in vitro studies. DHT synthesis from androstenedione in MCF-7 cells was significantly inhibited by coculture with aromatase-positive stromal cells, which was significantly reversed by addition of aromatase inhibitor exemestane. These results suggest that intratumoral DHT concentration is mainly determined by 5alphaRed1 and aromatase in breast carcinoma tissues, and antiproliferative effect of DHT may primarily occur in the cases positive for both AR and 5alphaRed1. Aromatase inhibitors may be more effective in these patients, possibly due to increasing local DHT concentration with estrogen deprivation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2006

Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis.

Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was negatively correlated with clinical stage, histological grade and HER2 status, and positively associated with sex-steroid receptors, steroidogenic acute regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal carcinoma in situ. These results suggest that LRH-1 is frequently detected in breast carcinoma tissues, and plays important roles including the regulation of in situ steroidogenesis.

Breast Neoplasms↗

PubMed2006

Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor-positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Comparison of MDCT and MRI for evaluating the intraductal component of breast cancer.

OBJECTIVE: The purpose of our study was to compare the accuracy of MDCT and MRI for evaluating the intraductal component of breast cancer. MATERIALS AND METHODS: Sixty-nine patients with histologically proven invasive carcinoma underwent MDCT and MRI. Retrospectively, two radiologists performed a blinded review of the MDCT and MRI. Cases with intraductal component enhancement were classified into two morphologic types: ductal extension and segmental distribution. The lengths of the main tumor and of the intraductal component were measured in cases with ductal extension. For cases with segmental distribution, only the maximum length of the tumor was measured. RESULTS: The sensitivity, specificity, and accuracy in detecting the intraductal component were 61%, 88%, and 71%, respectively, using MDCT; and 75%, 88%, and 80%, respectively, using MRI. MRI revealed the presence of the intraductal component with significantly higher sensitivity than did MDCT (p = 0.031). In the analysis of the length of the intraductal component in cases with ductal extension, which had relatively small intraductal components, underestimation by 15 mm or more was significantly less frequent with MRI than with MDCT (p = 0.008). There was no significant difference between MDCT and MRI in the evaluation of the maximum length of tumors in cases with segmental distribution, which had relatively large intraductal components. CONCLUSION: Compared with MDCT, MRI revealed the presence of the intraductal component with higher sensitivity and equivalent specificity. In cases with ductal extension, MRI is more precise than MDCT for determination of the margin for surgical removal, with less underestimation of the extent of the intraductal component.

Adult↗

PubMed2005

Estrogen-responsive finger protein as a new potential biomarker for breast cancer.

PURPOSE: Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor alpha. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables. EXPERIMENTAL DESIGN: Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax. RESULTS: Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor alpha status and negatively correlated with histologic grade or 14-3-3sigma immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker. CONCLUSIONS: Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.

14-3-3 Proteins↗

PubMed2005

Interactions between prostaglandin E(2), liver receptor homologue-1, and aromatase in breast cancer.

Local synthesis of estrogens within breast adipose tissue by cytochrome P450 aromatase contributes to the growth of postmenopausal breast cancers. One of the major stimulators of aromatase expression in breast is prostaglandin E(2) (PGE(2)) derived from tumorous epithelium and/or infiltrating macrophages. Recently, the orphan nuclear receptor, liver receptor homologue-1 (LRH-1), has also been shown to regulate aromatase expression in breast adipose tissue. We therefore examined the expression of, and correlations between, aromatase and LRH-1 mRNA in a panel of breast carcinoma tissues and adjacent adipose tissue. LRH-1 mRNA expression was low in normal breast tissue but markedly elevated in both breast carcinoma tissue and adipose tissue surrounding the tumor invasion (thereby paralleling aromatase expression). Laser capture microdissection localized the site of LRH-1 expression to tumor epithelial cells but not to intratumoral stromal cells. A strong correlation between LRH-1 and aromatase mRNA levels was observed in tumor-containing adipose tissue but not in tumor tissue. Ectopic expression of LRH-1 in primary human adipose stromal cells strongly activated endogenous aromatase mRNA expression and enzyme activity. Finally, treatment of adipose stromal cells with PGE(2) induced expression of both LRH-1 and aromatase. We suggest that PGE(2) derived from breast tumor tissue may increase aromatase expression in the surrounding adipose stroma in part by inducing LRH-1 in these cells. The roles of LRH-1 in breast cancer proliferation merit further study.

Adipose Tissue↗

PubMed2005

Breast conserving surgery with primary volume replacement using a lateral tissue flap.

Breast conserving surgery (BCS) is now a standard surgical treatment for early breast cancer. The number of patients with tumors under 3 cm who underwent breast conserving surgery overtook the number of patients who underwent total mastectomy for the first time in Japan in 2003. We have been employing breast conserving surgery with primary reconstruction using a lateral tissue flap (LTF), and have performed breast conserving surgery for 266 patients from 1990 to 2002. The incidence of local relapse was 5.6%. Although we did not irradiate a low risk group of 101 patients, our method is not inferior to other reports in which all cases underwent irradiation. Primary reconstruction with LTF has three advantages. The first is that we can avoid poly-surgery for breast reconstruction. The second is that the volume of the graft is maintained longer than reconstruction with a musculo-cutaneous flap. The third is that patients can avoid allergic reactions or granulomas as seen with artificial prosthesies. In conclusion, breast conserving surgery with immediate volume replacement with a LTF is a reasonable surgical procedure and has the advantage of avoiding unnecessary surgical procedures for reconstruction and surgical invasion without delaying the diagnosis of local relapse. Moreover, an adequate assessment of risk can spare low risk groups irradiation.

Axilla↗

PubMed2005

Pathological aspects of core needle biopsy for non-palpable breast lesions.

Recently, the incidence of non-palpable or noninvasive breast cancer has increased. Consequently, criteria for choosing procedures to obtain pathological materials had changed. Fine needle aspiration biopsy cytology (FNA) and core needle biopsy (CNB) are both reliable procedures for detecting breast cancer. However, for non-palpable lesions, the diagnostic accuracy of CNB is higher. The main limits of FNA are the high rate of insufficient sampling and inability to determine invasiveness. CNB is an established alternative to surgical biopsy, and CNB can avoid excess surgical biopsies in a large number of patients. In addition to accurate histological diagnosis, there is interest in obtaining prognostic information from CNB, especially for patients being considered for preoperative (neoadjuvant) therapy. CNB provides useful information about histologic type and grade. However, an unavoidable problem of CNB is underestimation of invasion. On the other hand, there is good concordance in particular for estrogen receptor (ER) and progesterone receptor (PR) between CNB and surgical excision. Several aspects of CNB remains controversial, such as diagnosing papillary lesions by CNB, problems regarding tumor cell displacement after CNB, and management of lobular neoplasia (LN) on CNB.

Biopsy, Needle↗

PubMed2005

Long-term outcome of breast-conserving therapy for breast cancer.

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.

Adult↗

PubMed2004

Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor.

Estrogen-related receptor alpha (ERRalpha) was identified as a gene related to estrogen receptor alpha (ERalpha) and belongs to a class of nuclear orphan receptors. ERRalpha binds to estrogen responsive element(s) (ERE) and is considered to be involved in modulation of estrogenic actions. However, biological significance of ERRalpha remains largely unknown. Therefore, we examined the expression of ERRalpha in human breast carcinoma tissues using immunohistochemistry (n = 102) and real-time reverse transcription-PCR (n = 30). ERRalpha immunoreactivity was detected in the nuclei of carcinoma cells in 55% of breast cancers examined, and relative immunoreactivity of ERRalpha was significantly (P = 0.0041) associated with the mRNA level. Significant associations were detected between ERalpha and ERE-containing estrogen-responsive genes, such as pS2 (P < 0.0001) and EBAG9/RCAS1 (P = 0.0214), in breast carcinoma tissues. However, no significant association was detected between ERalpha and pS2 (P = 0.1415) in the ERRalpha-positive cases (n = 56) or between ERalpha and EBAG9/RCAS1 (P = 0.8271) in the ERRalpha-negative group (n = 46). ERRalpha immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- (P = 0.0097 and P = 0.0053, respectively) and multi- (P = 0.0215 and P = 0.0118, respectively) variate analyses. A similar tendency was also detected in the group of breast cancer patients who received tamoxifen therapy after surgery. Results from our study suggest that ERRalpha possibly modulates the expression of ERE-containing estrogen-responsive genes, and ERRalpha immunoreactivity is a potent prognostic factor in human breast carcinoma.

Adult↗

PubMed2004

Collaboration of breast cancer clinic and genetic counseling division for BRCA1 and BRCA2 mutation family in Japan.

BACKGROUND: BRCA1 and BRCA2 mutations cause high breast cancer incidence rates as high as 80% Although prophylactic therapy is still controversial, several prophylactic therapies have been proposed and tried for BRCA1 and BRCA2 mutation carriers. Prophylactic surgery, chemo-prevention and precise screening have been proposed as prophylactic therapy. All BRCA1 and BRCA2 mutation carriers need knowledge about their disease and the countermeasures that are used to protect against onset of disease. Counseling plays an important role in this regard for people with genetic diseases. Therefore, collaboration between breast cancer clinics and genetic counseling services is the most important issue in clinical practice. Our group consists of three national universities and a general hospital. In this article we describe our trial to construct a clinical system against hereditary breast cancer as an interim report for the Japanese Ministry of Health, Labour and Welfare. PATIENTS AND METHODS: Twenty familial breast cancer patients were registered in this study. The whole sequence of BRCA1 and BRCA2 were analyzed. If pathological mutations were detected, their first degree families were introduced to the counseling division at each institute when candidates visited counseling divisions. RESULTS AND DISCUSSION: Four cases of a deleterious mutation in BRCA1 or BRCA2 were detected among 20 cases. Their first degree relatives are now under consideration for visiting counseling divisions. The clinical system described in this study should play a role to protect BRCA1 or BRCA2 mutation carriers in Japan.

Breast Neoplasms↗

PubMed2004

Biophoton detection as a novel technique for cancer imaging.

Biophoton emission is defined as extremely weak light that is radiated from any living system due to its metabolic activities, without excitation or enhancement. We measured biophoton images of tumors transplanted in mice with a highly sensitive and ultra-low noise CCD camera system. Cell lines employed for this study were AH109A, TE4 and TE9. Biophoton images of each tumor were measured 1 week after carcinoma cell transplantation to estimate the tumor size at week 1 and the biophoton intensity. Some were also measured at 2 and 3 weeks to compare the biophoton distribution with histological findings. We achieved sequential biophoton imaging during tumor growth for the first time. Comparison of microscopic findings and biophoton intensity suggested that the intensity of biophoton emission reflects the viability of the tumor tissue. The size at week 1 differed between cell lines, and the biophoton intensity of the tumor was correlated with the tumor size at week 1 (correlation coefficient 0.73). This non-invasive and simple technique has the potential to be used as an optical biopsy to detect tumor viability.

Animals↗

PubMed2003

Isolation of temperature-sensitive p53 mutations from a comprehensive missense mutation library.

Temperature-sensitive (ts) mutations have been used as a genetic and molecular tool to study the functions of many gene products. Each ts mutant protein may contain a temperature-dependent intramolecular mechanism such as ts conformational change. To identify key ts structural elements controlling the protein function, we screened ts p53 mutants from a comprehensive mutation library consisting of 2,314 p53 missense mutations for their sequence-specific transactivity through p53-binding sequences in Saccharomyces cerevisiae. We isolated 142 ts p53 mutants, including 131 unreported ts mutants. These mutants clustered in beta-strands in the DNA-binding domain, particularly in one of the two beta-sheets of the protein, and 15 residues (Thr155, Arg158, Met160, Ala161, Val172, His214, Ser215, Pro223, Thr231, Thr253, Ile254, Thr256, Ser269, Glu271, and Glu285) were ts hot spots. Among the 142 mutants, 54 were examined further in human osteosarcoma Saos-2 cells, and it was confirmed that 89% of the mutants were also ts in mammalian cells. The ts mutants represented distinct ts transactivities for the p53 binding sequences and a distinct epitope expression pattern for conformation-specific anti-p53 antibodies. These results indicated that the intramolecular beta-sheet in the core DNA-binding domain of p53 was a key structural element controlling the protein function and provided a clue for finding a molecular mechanism that enables the rescue of the mutant p53 function.

Amino Acid Sequence↗

PubMed2003

Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma.

Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, whereas steroid sulfatase (STS) hydrolyzes estrone sulfate to estrone. Both EST and STS have been suggested to play important roles in regulating the in situ production of estrogens in human breast carcinoma tissues. However, the expression of EST has not been examined in breast carcinoma tissues, and the biological significance of EST and STS remains unknown. Therefore, in this study, we examined the expression of EST and STS in 35 specimens of human breast carcinoma tissues using immunohistochemistry, reverse transcription-PCR (RT-PCR), and enzymatic assay. EST and STS immunoreactivity was also correlated with various clinicopathological parameters, including prognosis to examine the biological significance of these enzymes in 113 breast carcinomas. EST and STS immunoreactivity was detected in carcinoma cells and significantly associated with their mRNA levels (P = 0.0027 and 0.0158, respectively), as measured by RT/real-time PCR, and enzymatic activities (P = 0.0005 and 0.0089, respectively) in 35 breast carcinomas. In breast cancer tissues examined by laser capture microdissection/RT-PCR analyses, the mRNA for EST was localized in both carcinoma and intratumoral stromal cells, whereas that of STS was detected only in carcinoma cells. Of the 113 invasive ductal carcinomas examined in this study, EST and STS immunoreactivity was detected in 50 and 84 cases (44.2 and 74.3%), respectively. In these cases, EST immunoreactivity was inversely correlated with tumor size (P = 0.003) or lymph node status (P = 0.0027). In contrast, STS immunoreactivity was significantly correlated with tumor size (P = 0.0047). Moreover, EST immunoreactivity was significantly associated with a decreased risk of recurrence or improved prognosis by both uni (P = 0.0044, and 0.0026, respectively) and multivariate (P = 0.0429 and 0.0149, respectively) analyses. STS immunoreactivity, however, was significantly associated with an increased risk of recurrence (P = 0.0118) and worsened prognosis (P = 0.0325) by univariate analysis. Results from our present study suggest that immunoreactivities for both EST and STS are associated with their mRNA level and enzymatic activity and that EST immunoreactivity is considered to be a potent prognostic factor in human breast carcinoma.

Adult↗

PubMed2003

Intracrine mechanism of estrogen synthesis in breast cancer.

It has been demonstrated that biologically active estrogens are locally produced from circulating inactive steroids in an intracrine mechanism in the breast carcinoma. The in situ production of estrogens is considered to play an important role in the proliferation of breast cancer cells, especially in the postmenopausal women. Therefore, the total blockade of this pathway may lead to an improvement in the prognosis in breast cancer patients due to the inhibition of estrogenic actions. In this review, we describe the recent studies of enzymes related to intracrine mechanism of estrogen synthesis, including aromatase, steroid sulfatase (STS), and 17beta-hydroxysteroid dehydrogenase, in human breast carcinoma tissues, and discuss the biological significance of local production of estrogens in human breast cancer.

17-Hydroxysteroid Dehydrogenases↗

PubMed2003

Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma.

Steroid sulfatase (STS) hydrolyzes inactive estrone sulfate (E1-S) to estrone (E1), while estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to estrogen sulfates. They are considered to play important roles in the regulation of local estrogenic actions in various human tissues, however, their biological significance remains largely unknown. Therefore, we examined the expression of STS and EST in non-pathologic human tissues and breast carcinomas. STS expression was very weak except for the placenta, while EST expression was markedly detected in various tissues examined. In breast carcinoma tissues, STS and EST immunoreactivity was detected in carcinoma cells in 74 and 44% of cases, respectively, and was significantly associated with their mRNA levels and enzymatic activities. STS immunoreactivity was significantly correlated with the tumor size, and an increased risk of recurrence. EST immunoreactivity was inversely correlated with the tumor size or lymph node status. Moreover, EST immunoreactivity was significantly associated with a decreased risk of recurrence or improved prognosis. Our results suggest that EST is involved in protecting various peripheral tissues from excessive estrogenic effects. In the breast carcinoma, STS and EST are suggested to play important roles in the regulation of in situ estrogen production in the breast carcinomas.

Breast Neoplasms↗

PubMed2003

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases.

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.

Adult↗

PubMed2003

Pathological assessment of intraductal spread of carcinoma in relation to surgical margin state in breast-conserving surgery.

BACKGROUND: Spreading of carcinoma has been considered to be a prognostic factor for local failure after breast-conserving therapy. The extensive intraductal component (EIC) was defined as when the component of intraductal carcinoma constitutes more than 25% of the primary tumor with intraductal foci. However, the definition of EIC was based on the predominance of intraductal component surrounding the invasive lesions and not on the segmental anatomy. We designated carcinoma extension as the intraductal spread of carcinoma (ISC) along with the duct-lobular system by three-dimensional (3-D) reconstruction analysis. This study was initiated to simplify the method of two-dimensional (2-D) pathological examination based on 3-D mapping. METHODS: Thirty-four specimens from breast cancer patients were subjected to 3-D reconstruction. We investigated the correlation between actual extension of intraductal carcinoma and EIC defined by 2-D examination or ISC grading defined by 3-D reconstruction. Furthermore, using another 62 histological mappings, we investigated how correctly the simplified 2-D method using several paraffin blocks reflected the actual carcinoma spread and margin state. RESULTS: Carcinoma extension over 2 cm was observed in 64% specimens that were EIC positive and 26% specimens that were EIC negative. In contrast, according to the ISC grading defined by 3-D reconstruction, none of the specimens with a low grade of ISC demonstrated carcinoma extension over 2 cm. Carcinoma extension over 2 cm was observed in 71% of specimens with a high grade of ISC, thus demonstrating a correlation between carcinoma extension and ISC grading. In addition, the simplified 2-D method using only several blocks reflected both the 3-D ISC grading and surgical margin state. CONCLUSIONS: We conclude that ISC grading correlates with carcinoma extension and surgical margin state. From a clinical point of view, the simplified 2-D examination using paraffin blocks may contribute to routine surgical pathology in evaluating the degree of carcinoma extension in breast-conserving therapy.

Adult↗