A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using multicatheter interstitial brachytherapy: clinical results with a median follow-up of 60 months.

BACKGROUND: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan. METHODS: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered. RESULTS: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm3 (range 28-260 cm3). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm3 and 76.3 ± 45.6 cm3, respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004. CONCLUSIONS: This study showed excellent local control and survival results with minimal late sequelae.

Case report of a dose-volume histogram analysis of rib fracture after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

We initiated the first multi-institutional prospective study of accelerated partial breast irradiation for early breast cancer in Japan. Our early clinical results showed that the treatment methods were technically reproducible between institutions and showed excellent disease control at a median follow-up of 26 months in our previous report. At present, total 46 patients from six institutions underwent the treatment regimen from October 2009 to December 2011, and the median follow-up time was 60 months (range, 57-67 months). In 46 patients, we experienced one patient who had rib fracture as a late complication. The dose-volume histogram (DVH) result of this patient was analyzed. The D0.01cc, D0.1cc, and D1cc values of the patient were 913, 817, and 664 cGy per fraction, respectively. These values were the highest values in 46 patients. The average D0.01cc, D0.1cc, and D1cc values of the other 45 patients were 546, 500, and 419, respectively, cGy per fraction. From this result, DVH values showing high-dose irradiated volume (D0.01cc, D0.1cc, and D1cc) seem to be a good predictive factor of rib fracture for accelerated partial breast irradiation. However, further investigation is necessary because of the small number of patients investigated.

Uncertainty of cosmetic evaluation after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

PURPOSE: We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here. MATERIALS AND METHODS: Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0. RESULTS: No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher. CONCLUSION: APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000001677.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.

BACKGROUND: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months. PATIENTS AND METHODS: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0. RESULTS: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively. CONCLUSIONS: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: treatment planning and quality assurance.

BACKGROUND: In Japan, breast-conserving surgery with closed cavity has generally been performed for breast cancer patients, and accelerated partial breast irradiation (APBI) is considered difficult because Asian females generally have smaller breast sizes than Western females. Therefore, common identification of target and treatment plan method in APBI is required. A prospective multicenter study was conducted in Japan to determine institutional compliance with APBI using high-dose-rate interstitial brachytherapy (ISBT) designed for Japanese female patients. METHODS: For this study, 46 patients were recruited at eight institutions from January 2009 to December 2011. The reproducibility of the ISBT-APBI plan was evaluated using three criteria: (1) minimum clinical target volume dose with a clip dose ≥ 6 Gy/fraction, (2) irradiated volume constraint of 40-150 cm(3), and (3) uniformity of dose distribution, expressed as the dose non-uniformity ratio (DNR, V150/V100) < 0.35. The ISBT-APBI plan for each patient was considered reproducible when all three criteria were met. When the number of non-reproducible patients was ≤ 4 at study completion, APBI at this institution was considered statistically reproducible. RESULTS: Half of the patients (52 %) had a small bra size (A/B cup). The mean values of the dose-constrained parameters were as follows: Vref, 117 cm(3) (range, 40-282), DNR, 0.30 (range, 0.22-0.51), and clip dose, 784 cGy (range, 469-3146). A total of 43/46 treatment plans were judged to be compliant and ISBT-APBI was concluded to be reproducible. CONCLUSIONS: This study showed that multi-institutional ISBT-APBI treatment plan was reproducible for small breast patient with closed cavity.

Breast carcinoma originating from a silicone granuloma: a case report.

Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.

Breast ultrasound elastography and magnetic resonance imaging of fibrotic changes of breast disease: correlations between elastography findings and pathologic and short Tau inversion recovery imaging results, including the enhancement ratio and apparent diffusion coefficient.

PURPOSE: Ultrasound (US) elastography provides information regarding tissue hardness and is expected to become a novel diagnostic tool for breast disease. In contrast, magnetic resonance (MR) images reflect the tissue characteristics. Fibrosis of the stroma of breast diseases may affect their hardness. We investigated the correlation among elasticity score (ES) and signal intensity of short Tau inversion recovery MR images, enhancement ratio, apparent diffusion coefficient (ADC), and the fibrosis in the breast lesions. MATERIALS AND METHODS: We reviewed the findings of US elastography and MR imaging from 41 consecutive patients with breast lesions (25 invasive ductal carcinoma, 3 fibroadenoma, 1 phyllodes tumor, 2 ductal hyperplasia, 2 primary malignant lymphoma, 3 mastopathy, 1 metastasis, 1 tubular adenoma, 1 ductal carcinoma in situ, 1 diabetic mastopathy, and 1 intraductal papilloma). In each patient, elastography images were classified based on Tsukuba ES. We calculated the ratio of signal intensity of the lesion to the muscle on short Tau inversion recovery images (L/M ratio), enhancement ratio of early to precontrast and early to delayed images, and ADC for each lesion. The ES and MR findings were correlated with the degree of fibrosis (based on Masson trichrome stain). RESULTS: The ES significantly correlated with the L/M ratio (P = 0.0306) and the ADC (P = 0.0256). The stromal fibrosis also correlated with ES (P = 0.0023), the L/M ratio (P = 0.0344), and enhancement ratio of the early-to-delayed images (P = 0.049). CONCLUSIONS: The ES and L/M ratio are correlated significantly with each other, and they are correlated with the fibrosis. These results suggest that they will provide the information on the fibrosis and may help the diagnosis of breast lesions.

Primary breast peripheral T-cell lymphoma not otherwise specified: report of a case.

Malignant lymphomas of the breast are rare and primary breast lymphoma comprises <0.5 % of breast malignancies, within which T-cell lymphomas are an even rarer subset. We report a case of primary breast peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). Histology of the biopsied specimen revealed CD2(+), CD3(+), CD4(+), CD5(-), CD7(+), CD8(-), CD20(-), CD25(-), CD30(+), CD56(-), bcl-2(-), EBV-ISH(-), TIA-I(-), and ATLA negative. The patient was treated with six cycles of the CHOP regimen and died 17 months after the diagnosis was made, despite complete remission after conventional chemotherapy. To our knowledge, only 18 cases of primary peripheral T-cell lymphoma of the breast and just one previous case of primary PTCL-NOS of the breast have been reported in Japan.

Lung adenocarcinoma metastasis to the male breast: a case report.

We report the case of a 60-year-old male patient who was diagnosed with metastasis from primary lung cancer to the breast. The patient presented with a mass in the right breast. Mammography, ultrasound, and magnetic-resonance imaging each suggested primary breast cancer. A core-needle biopsy of the right breast mass indicated poorly differentiated adenocarcinoma. A basic chest X-ray showed a shadow in the left upper lung. Thoraco-abdominal computed tomography revealed a mass with a diameter of 90 mm in the left superior region, the shape of which was indicative of primary lung cancer. A lung biopsy confirmed poorly differentiated adenocarcinoma. We diagnosed primary lung cancer with metastases to the bone, brain and right breast (cT2N3M1, stage IV) by imaging and histopathology. He was administered carboplatin (area under the curve 6 mg / ml) and paclitaxel (200 mg / m(2)) tri-weekly, and underwent gamma-knife treatment for the brain metastasis. The treatments reduced the primary tumor and the metastases. However, after completion of the fifth treatment cycle, he developed disseminated intravascular coagulation from septic shock, and died on the eleventh day after completing the fifth cycle of treatment. Although metastasis to the mammary gland is uncommon, especially among males, metastasis to the mammary gland should be considered when a mammary mass does not exhibit the typical characteristics of breast cancer. A correct diagnosis of metastasis to the mammary gland from lung cancer makes it possible to select the most appropriate treatment method.

Usefulness of endoscopic breast-conserving surgery for breast cancer.

PURPOSE: We compared the safety, invasiveness and cosmetic outcomes between endoscopic breast-conserving surgery (endoscopic group) and surgery under direct vision (direct vision group) for treating breast cancer. METHODS: We compared 100 cases of endoscopic surgery with 150 cases of direct vision surgery. The safety was evaluated in terms of the blood loss, length of the operation and presence or absence of complications, whereas the degree of invasiveness was assessed using preoperative and postoperative leukocyte counts, neutrophil counts, interleukin (IL-6) levels and fever. The cosmetic outcome was assessed on the basis of a breast evaluation by the medical staff and the patient's subjective satisfaction. RESULTS: In both groups, serious postoperative complications were absent. No significant differences were observed in the leukocyte counts, neutrophil counts, IL-6 level or fever between the groups. An evaluation of the cosmetic outcomes by the staff showed a more favorable breast size, breast shape and scar condition in the endoscopic group. A significantly higher level of patient satisfaction was also observed in the endoscopic group. Postoperative local recurrence was absent. CONCLUSIONS: The endoscopic approach showed comparable safety and invasiveness, and provided better postoperative cosmetic outcomes than direct vision surgery. Our results suggest that endoscopic breast-conserving surgery is a potentially useful surgical method for the treatment of breast cancer.

Synthesis of a resin monomer-soluble polyrotaxane crosslinker containing cleavable end groups.

A resin monomer-soluble polyrotaxane (PRX) crosslinker with cleavable end groups was synthesized to develop degradable photosetting composite resins. The PRX containing 50 α-cyclodextrins (α-CDs) with disulfide end groups was initially modified with n-butylamine to obtain a resin monomer-soluble PRX. The PRX containing 13 n-butyl groups per α-CD molecule was completely soluble in conventional resin monomers such as 2-hydroxyethyl methacrylate (HEMA) and urethane dimethacrylate (UDMA). The synthesized n-butyl-containing PRX was further modified with 2-aminoethyl methacrylate to provide crosslinkable acrylic groups onto PRX. The prepared resin monomer-soluble PRX crosslinker was successfully polymerized with a mixture of HEMA and UDMA to provide photosetting plastic. It was confirmed that the Vickers hardness of the prepared plastic was greatly decreased after treatment with dithiothreitol. This indicates that the resin monomer-soluble PRX crosslinker can be applied to design degradable photosetting plastics potentially used in the industrial or biomedical field.

FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis.

The forkhead box protein 3 (FOXP3) transcription factor is highly expressed in tumor cells as well as in regulatory T cells (Tregs). It plays a tumor-enhancing role in Tregs and suppresses carcinogenesis as a potent repressor of several oncogenes. The clinical prognostic value of FOXP3 expression has not yet been elucidated. In this study, immunohistochemistry was used to investigate the prognostic significance of FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in breast cancer patients. Of the 100 tumor specimens obtained from primary invasive breast carcinoma, 63 and 57% were evaluated as FOXP3+ tumor cells and as being highly infiltrated by FOXP3+ lymphocytes, respectively. Although FOXP3 expression in tumor cells was of no prognostic significance, FOXP3+ lymphocytes were significantly associated with poor overall survival (OS) (n=98, log-rank test P=0.008). FOXP3 exhibited a heterogeneous subcellular localization in tumor cells (cytoplasm, 31%; nucleus, 26%; both, 6%) and, although cytoplasmic FOXP3 was associated with poor OS (P= 0.058), nuclear FOXP3 demonstrated a significant association with improved OS (P=0.016). Furthermore, when patients were grouped according to their expression of tumor cytoplasmic FOXP3 and lymphocyte FOXP3, there were notable differences in the Kaplan-Meier curves for OS (P<0.001), with a high infiltration of FOXP3+ lymphocytes accompanied by a cytoplasmic FOXP3+ tumor being the most detrimental phenotype. These findings indicated that FOXP3 expression in lymphocytes as well as in tumor cells may be a prognostic marker for breast cancer. FOXP3 in tumor cells may have distinct biological activities and prognostic values according to its localization, which may help establish appropriate cancer treatments.

Giant malignant phyllodes tumor: a case report.

We present a case of a 57-year-old woman with a giant malignant phyllodes tumor (PT) in her right breast, with maximum diameter of 20 cm. The core-needle and excisional biopsy specimens were diagnosed as suspicious for low-grade myofibroblastic sarcoma (LGMS). The subsequent total mastectomy with partial resection of the pectoral muscles showed predominance of stromal hypercellularity without an epithelial component. However, we diagnosed this as a malignant PT because focal areas showed a leaf-like pattern. In the case of large malignant PTs that exhibit stromal predominance, it can be difficult to distinguish between a pure sarcoma and malignant PT. It is important to thoroughly examine multiple sections from the view point of residual epithelial structure in morphological diagnosis.

Adenomyoepithelioma of the breast diagnosed by a mammotome biopsy: report of a case.

Adenomyoepithelioma is an uncommon primary breast tumor. It is conspicuous for two elements of the tumor, namely, ductal and myoepithelial components. Recently, a Mammotome biopsy, or stereotactic vacuum-assisted biopsy has become popular and various benign or borderline lesions are obtained. We report an adenomyoepithelioma of the breast in a 56-year-old woman. She was pointed out to have a cluster of some microcalcifications on mammography and a 9-mm hypoechoic mass lesion was detected by ultrasound. A Mammotome biopsy revealed a well-defined lesion. Histologically, the tumor demonstrated a thick and bi-cellular growth pattern consisting of ducts and myoepithelium. Immunohistochemically, epithelial cells were positive for cytokeratin AE1/AE3 and cytokeratin, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA), negative for alpha-smooth muscle actin (alpha-SMA). In addition, myoepithelial cells were positive for alpha-SMA and CEA, which were scatterly positive for cytokeratin AE1/AE3, and negative for EMA. In examinations of non-palpable lesions found on mammography and ultrasound, a Mammotome biopsy is useful for making diagnosis, however, and adenomyoepithelioma is rarely found. In diagnosing such a rare disease from the limited information obtained from a needle biopsy, an immunohistochemical study was thus found to be useful for making a differential diagnosis.

Preclinical studies of molecular-targeting diagnostic and therapeutic strategies against breast cancer.

We have investigated protein kinase C (PKC) signaling, a putative differentiation-related and metastasis suppressor gene Cap43/NDRG1/Drg-1, and Y-box binding protein-1 (YB-1) to identify new molecular targeting for breast cancer. PKC is a family of serine/threonine kinases that is involved in the regulation of cell growth. We have demonstrated that PKC caused G(1) arrest in a breast cancer cell line through a mechanism involving a PKC-ERK MAPK-JNK-Rb protein signaling pathway. We have also characterized a novel mechanism through which all-trans retinoic acid (ATRA) and antineoplaston, anticancer drug, caused cell growth inhibition in breast cancer cells through effects on intracellular pathways. ATRA decreased the expression of PKCalpha, as well as reduced ERK MAPK phosphorylation, and consequently caused G(1) arrest. Antineoplaston caused the down-regulation of PKCalpha protein expression, resulting in inhibition of ERK MAPK phosphorylation, with resultant inhibition of Rb phosphorylation leading to G(1) arrest. PKC signaling represents a promising target for development of novel therapeutic agents. Cap43 is known as N-myc downstream-regulated gene 1 (NDRG1). Treatment with estradiol (E(2)) significantly decreased the expression of Cap43 in ER-alpha-positive breast cancer cell lines. Co-administration of tamoxifen abrogated the E(2)-induced downregulation of Cap43 in ER-alpha-positive cell lines. These results suggested that Cap43 may hold the potential of being a molecular marker to determine the therapeutic efficacy of anti-estrogenic anticancer agents in breast cancer. YB-1 is a member of the cold shock domain protein family. The expression of nuclear YB-1 was correlated with HER2 positively in clinical specimens of human breast cancer. Immunostaining studies showed that nuclear YB-1 expression was an independent prognostic factor of overall survival. Expression of nuclear YB-1 played an essential role in acquirement of malignant characteristics through HER2-dependent pathways in breast cancer patients. PKC, Cap43 and YB-1 may be useful in new molecular-targeting diagnosis and therapeutics in breast cancer.

Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case.

We report a case of axillary lymph node recurrence of thyroid papillary microcarcinoma (PMC) in a 51-year-old woman who had undergone thyroidectomy with lymph node dissection 5 years earlier. We performed residual thyroid resection with cervical and bilateral axillary lymph node dissection, and pathological examination revealed well-differentiated papillary carcinoma, with partial poor differentiation. Postoperative radioiodine therapy was ineffective, and the patient died of systemic dissemination of the recurrence 8 months after her second operation. The positive cell rates of proliferating cell nuclear antigen and Ki-67 were clearly higher in the recurrent lymph nodes than in the primary thyroid tumor, suggesting increased cell proliferation in the recurrent lymph nodes. Thyroid papillary carcinoma rarely recurs in the axillary lymph nodes, but its possibility must be kept in mind, especially in patients with remarkable cervical lymph node metastasis and those who undergo extensive lymph node dissection.

Cell growth inhibition by all-trans retinoic acid in SKBR-3 breast cancer cells: involvement of protein kinase Calpha and extracellular signal-regulated kinase mitogen-activated protein kinase.

All-trans retinoic acid (ATRA), a synthetic derivative of vitamin A, inhibits the growth of breast cancer cells. To elucidate the mechanism by which ATRA causes cell growth inhibition, we examined changes in cell cycle and intracellular signaling pathways, focusing on protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). Using the estrogen receptor-negative, retinoid receptor-positive breast cancer cell line SKRB-3, we found that treatment with ATRA significantly decreased the expression of PKCalpha, as well as reducing ERK MAPK phosphorylation. ATRA treatment leads to dephosphorylation of Rb, and consequently to G(1) arrest. Marked changes in the expression of cyclins (particularly cyclins A and E) were observed in SKBR-3 cells treated with ATRA. Using a series of pharmacological and molecular approaches, we found evidence that ATRA-induced SKBR-3 cell growth inhibition involves the deregulation of the PKCalpha-MAPK pathway. These data suggest that retinoids interfered with signal transduction pathways that are crucial for cell cycle progression, and highlight the complexities of the biological effects of retinoid derivatives.

Relationship between microvessel density and thermographic hot areas in breast cancer.

PURPOSE: This study was conducted to evaluate the validity of thermography in breast examination. METHODS: We performed contact thermography and measured the direct temperature by inserting a needle-type thermometer into the tissue. The core temperature of the tumor (dTt) and the temperature of the tissue surrounding the tumor (dTs) were compared with normal tissue. The microvessel density (MVD) and the MIB-1 labeling index (MIB-1 LI) of the tumor were examined immunohistochemically. The subjects were 48 women with primary invasive ductal carcinoma. The area of the tumor was diagnosed pathologically, and the hot area was measured using thermography. RESULTS: The dTt was significantly higher than the dTs. Both the dTt and dTs were significantly higher when the thermographical hot area was positive, or when more than four lymph node metastases were found. The dTs was correlated with MVD. A correlation between MVD and tumor temperature measured directly was also confirmed. A higher dTs was related to the dissociated wide area of the thermogram. CONCLUSION: These findings suggested a relationship between dTs and the high-risk group of breast cancer. We also found that abnormalities in temperature were reflected in thermography and that a higher dTs was related to the dissociated wide area of the thermogram.

Immunohistological study of cell cycle-related factors, oncogene expression, and cell proliferation in adenocarcinoma developed in Barrett's esophagus.

In addition to presenting clinicopathological findings in 3 patients with adenocarcinoma developed in Barrett's esophagus, we have investigated the expression of cell cycle-related factors, oncogenes and cell proliferation in normal squamous epithelium, specialized columnar epithelium (SCE) and adenocarcinoma in Barrett's esophagus, using immunohistological techniques. The expression of p21 in adenocarcinoma in Barrett's esophagus tended to be decreased in two mutated p53-strongly-positive patients and to be increased in one mutated p53-weakly-positive patient. Furthermore, mutated p53 was strongly expressed in the deep layer of the cancer, while p21 was expressed in the superficial layer of the cancer. Thus, mutated p53 was inversely correlated with p21 in adenocarcinoma in Barrett's esophagus. The mean positive cell rate (PR) of Ki-67 was 4% in normal squamous epithelium, 24.5% in the SCE, and 41.7% in the adenocarcinoma in Barrett's esophagus. The mean PR of proliferating cell nuclear antigen (PCNA) was 6% in normal squamous epithelium, 29.5% in the SCE, and 55% in the adenocarcinoma in Barrett's esophagus. Thus, the PR of Ki-67 and PCNA were clearly higher in the SCE in Barrett's esophagus than in normal squamous epithelium, indicating increased cell proliferation in the SCE in Barrett's esophagus. In conclusion, mutated p53 was inversely correlated with p21 in adenocarcinoma in Barrett's esophagus. p53 mutation and the expression of oncogenes such as c-erbB-2 and MDM2 were observed in the SCE in Barrett's esophagus, which showed higher cell proliferation than normal squamous epithelium, suggesting a high malignant potential of the SCE in Barrett's esophagus. We considered that it was important to carefully follow-up patients with Barrett's esophagus.