Hiroko Kawashima

Gene amplification of ESR1 in breast cancers-fact or fiction? A fluorescence in situ hybridization and multiplex ligation-dependent probe amplification study

Oestrogen receptor‐alpha (ERα), encoded by the ESR1 gene located on 6q25, is a nuclear transcription factor. Since it was reported in 2007 that more than 20% of breast cancers show ESR1 gene amplification, there has been considerable controversy about its frequency and clinical significance. We set out to assess the frequency and levels of ESR1 amplification in breast cancers. In a total of 106 breast needle biopsy specimens examined by immunohistochemistry, 78 tumours contained more than 10% ERα‐positive cancer cells. In fluorescence in situ hybridization (FISH) analysis with an ESR1‐specific probe, variously extended ESR1 signals were found in ERα‐expressing cells. Some of these were indistinguishable from large clustered signals generally accepted to mean high‐level gene amplification in homogeneously staining regions (HSRs), and could be considered to represent gene amplification. However, with RNase treatment, the ‘HSR‐like’ signals changed to small compact signals, and are thus thought to represent concentrated RNA. FISH using two differently labelled probes corresponding to the non‐overlapping 5′‐ and 3′‐end portions of the ESR1 gene on touch smears showed a preserved spatial relationship of the 3′ to 5′ sequence of ESR1, therefore strongly suggesting that the RNA consisted of primary transcripts. Using touch smears obtained from 51 fresh tumours, precise enumeration of ESR1 signals with a correction by the number of centromere 6 on FISH after RNase A treatment revealed that three tumours (5.9%) had tumour cells with one to three additional copies of ESR1 as predominant subpopulations. This infrequent and low level of gene amplification of ESR1 was also detected as a ‘gain’ of the gene by analysis with multiplex ligation‐dependent probe amplification (MLPA). The consistent results from immunohistochemistry, FISH, and MLPA in the present study settle the long‐standing debate concerning gene amplification of ESR1 in breast carcinoma. Copyright

The role of axillary lymph node dissection in breast cancer management

Although it is generally accepted that axillary dissection provides no survival advantage in patients with breast cancer, it is commonly regarded as a reliable method of assessing nodal status and treating regional disease. However, it is time to consider eliminating routine axillary dissection in patients who are clinically node-negative. A sentinel lymph node biopsy may assess axillary nodal status while obviating a full axillary dissection. At present, axillary dissection remains the standard approach for the surgical management of all patients with invasive carcinoma of the breast, regardless of tumor size or patient age, though it is unnecessary for patients with small intraductal carcinomas.

Pathologic Assessment of Surgical Margins on Frozen and Permanent Sections in Breast Conserving Surgery

The diagnostic value of frozen section was evaluated in the histologic assessment of surgical margins obtained by wide excision of breast tumors. There were 87 patients with unilateral breast cancer, and 5 with bilateral breast cancers. The periphery of the excised breast tissue was peeled like an orange and histologically examined by frozen and permanent section. If eitherin situ or infiltrating microscopic tumor was found at the margin, it was considered positive. Using frozen sections, the margin was judged histologically positive or suspicious in 30 tumors (31%) and negative in 67 (69%) tumors. Positive surgical margins were histologically confirmed by permanent section in 20 (67%) of the 30 tumors diagnosed as positive or suspicious on frozen section. Another 10 tumors had negative margins. In 4 tumors, however, while the initial or re-excised margin was negative on frozen section, the margins were positive by permanent section. These surgical margins were positive due exclusively to the presence of ductal carcinomain situ (DCIS). Evaluation of surgical margins in breast cancer by frozen section, thus exhibited a diagnostic accuracy of 86%, a sensitivity of 83%, and a specificity of 86%. It is concluded that frozen sections are useful in the determination of involvement of surgical margins after the wide excision of breast cancer. It must be pointed out that frozen sections will often overestimate involvement of the surgical margins.

Breast cancer in dense breast: Detection with contrast‐enhanced dynamic MR imaging

The purpose of this study was to identify contrast enhancement patterns of dense breast parenchyma and to investigate the ability of dynamic magnetic resonance imaging (MRI) to detect cancer in the dense breast. Thirty‐two patients with breast cancer in dense breast underwent gadolinium‐enhanced dynamic MRI. The detectability of cancer by dynamic MRI, mammography, and physical examination was compared. Two parenchymal enhancement patterns could be identified. One was increasingly multiple patchy enhancement found predominantly in the periphery (type A), and the other was faint enhancement without any nodular opacification (type B). Type A was thought to reflect severe proliferative fibrocystic change (PFC). For both patterns, the detection rate of primary cancers by dynamic MRI was found to be superior to that by other modalities. Dynamic MRI also could detect multifocal cancers, which could not be found with other modalities, although the detectability of these small cancers might be reduced in patients with severe PFC. J. Magn. Reson. Imaging 2000;11:233–243.

Oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle, and axillary dissection followed by radiotherapy

We evaluated the oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a wide excision of breast tissue was performed to obtain tumor-free margins. The subsequent breast deformity was not corrected in six patients in the early phase of the study (Group 1), and in 16 patients in the late phase (Group 2) in which the breast deformity was not remarkable at the time of operation. Breast deformity was corrected by transposing adipose tissue with LDM on a vascular pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two patients developed distant metastases. None were found to have local recurrence. Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of the Group 3 patients had an excellent or good cosmetic result. However, when the cosmetic results were evaluated in patients who underwent transposition and had small breasts, the results were excellent or good in 76%, compared to 38% in the patients who had reconstructions who had large breasts. The difference was statistically significant (p = 0.0309). Therefore, it was confirmed that wide excision and axillary dissection followed by breast radiation could provide adequate local control, but frequently resulted in breast deformity. However, transposition of adipose tissue may be useful to correct the breast deformity, especially in women with small breasts.

Feeding artery of laryngeal and hypopharyngeal cancers: role of the superior thyroid artery in superselective intraarterial chemotherapy.

The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

Radioanatomical study of a true tracheal bronchus using multidetector computed tomography

PurposeTrue tracheal bronchus (TTB) is a rare anomaly in which a lobar or segmental ectopic bronchus arises from the trachea. We examined the frequency and multidetector computed tomography (MDCT) appearances of TTB.Materials and methodsWe retrospectively analyzed 9781 chest MDCT examinations. In cases in which there was an abnormal bronchus suggesting TTB on axial CT images, the following imaging of the abnormal bronchi was undertaken: multiplanar reformation (MPR), multiprojection volume reconstruction (MPVR), volume rendering (VR), and virtual endoscopy (VE).ResultsOf 9781 MDCT examinations, 30 TTBs were observed in 10 females and 20 males. The frequency of TTB was 0.21% among 4622 females, 0.39% among 5159 males (0.31 % in the overall patient population). TTBs arose from the right lateral wall of the trachea; 17 TTBs were of the displaced type and 13 of the supernumerary type. With the displaced type, all segments of the right upper lobe were supplied by the TTB in 8 patients, and the apical segment was supplied in 8 patients. With the supernumerary type, TTBs showed blind termination in 10 patients, and the TTB had a small lobule in 3 patients. All TTBs were clearly visualized on MPR, MPVR, VR, and VE.ConclusionTTB was identified by MDCT with an incidence of 0.31%.

Bloom's syndrome in a Japanese girl

Clinical, cytogenetic, and immunological data of a 5‐year‐old Japanese girl with Blooms syndrome are described. Growth deficiency, photosensitivity, and a very mild facial telangiectatic erythema were present. Cytological studies revealed chromosomal aberrations and the characteristic high frequency in sister chromatid exchanges. Immunological studies showed that the serum levels of IgM and IgA, but not IgG, were abnormally low as compared to the agematched control values and that the generation of cytoplasmic immunoglobulin‐producing cells in the peripheral blood lymphocytes, which was evaluated in the in vitro pokeweed mitogen‐stimulated cultures, was markedly reduced.

Two different types of ring-like enhancement on dynamic MR imaging in breast cancer: correlation with the histopathologic findings.

To describe two different types of “ring‐like enhancement” seen on dynamic magnetic resonance imaging (MRI) of breast cancer, and compare their histopathological features.

Triple-negative Breast Cancer: Are the Imaging Findings Different Between Responders and Nonresponders to Neoadjuvant Chemotherapy?

RATIONALE AND OBJECTIVES The purpose of the present study was to evaluate the imaging findings of triple-negative breast cancer patients receiving neoadjuvant chemotherapy (NAC) and to investigate whether the findings are different between responders and nonresponders, enabling us to predict the final patient response. MATERIALS AND METHODS The subjects included 22 women ages 35-73 years (mean, 50.4 years) with 23 triple-negative breast cancers who underwent NAC. In all cases, a mammography, ultrasound, and magnetic resonance imaging (MRI) were performed a total of three times: before NAC, after the first half of NAC, and after NAC. The mass shape, mass margin, presence of clear intratumoral necrosis, and presence of intratumoral calcification were analyzed. The presence of clear intratumoral necrosis was evaluated on the MRI. If there was a very high signal intensity (similar to that of water) in the tumor on the fat-suppressed T2-weighted MRI scans, we judged it to be clear intratumoral necrosis. RESULTS An irregularly shaped mass (P = .018) and the presence of clear intratumoral necrosis (P = .044) were significantly associated with NAC nonresponse in triple-negative breast cancer patients. The mass margin and the presence of intratumoral calcification were not related to the effects after NAC. CONCLUSIONS In cases of triple-negative breast cancer involving clear intratumoral necrosis with an irregular mass shape, it is predicted that the effects of neoadjuvant chemotherapy will likely be poor, and therefore, the presence of such image findings may be useful for determining the optimal application of neoadjuvant chemotherapy.