Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan.

The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma.

Concept and design of a nationwide prospective feasibility/efficacy/safety study of weekly paclitaxel for patients with pathologically confirmed anaplastic thyroid cancer (ATCCJ-PTX-P2).

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, often demonstrating resistance to multimodal therapeutic approaches. The median survival of ATC patients after initial diagnosis was reported to be <6 months due to the rapid progression of disease by dissemination and/or invasion. There have been several reports describing possible effective chemotherapies, but these studies might be biased by the nature of retrospective accumulations of clinical experiences, and thus reliable data concerning the efficacies of the treatment efforts are required. DESIGN: In 2009, we established the research organization Anaplastic Carcinoma Research Consortium Japan (ATCCJ) to investigate this highly malignant disease. Using this nationwide organization, we conducted a prospective clinical study to investigate the feasibility, safeness, and efficacy of chemotherapy with weekly paclitaxel for ATC patients. This trial is registered on the clinical trials site of the University Hospital Medical Information Network Clinical Trials Registry Web site (UMIN000008574). The study was started in 2012, and enrollment was closed in March 2014 after accumulating 71 patients from 28 registered institutes. The follow-up data will be available in April 2015. DISCUSSION: Important information concerning the management of this disease is expected to be revealed by this study. The concept and design of the study are described herein.

Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid cancer (DTC) in juvenile versus adult patients.

In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.

Biological differential diagnosis of follicular thyroid tumor and Hürthle cell tumor on the basis of telomere length and hTERT expression.

BACKGROUND: The most difficult thyroid tumors to diagnose by histology are follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). Telomere alteration and human telomerase reverse transcriptase (hTERT) expression have been observed in most human cancers and are known to be a feature of malignancy. The purpose of this study was to clarify whether hTERT protein expression and telomere alteration could be applicable biological markers for distinguishing FTC from HCC. METHODS: We investigated a total of 78 thyroid tumor cases, including 14 FTCs, 47 follicular adenomas (FTAs), 5 HCCs, and 12 Hürthle cell adenomas (HCAs). hTERT protein expression was examined by immunohistochemistry, and telomere length was determined by tissue quantitative fluorescence in situ hybridization. RESULTS: Positivity for hTERT protein expression was observed in 86 % of FTCs and 49 % of FTAs. Telomeres in FTCs were significantly shorter than those in FTAs. All HCCs and HCAs (100 %) expressed hTERT protein. Telomeres in HCCs were significantly shorter than those in HCAs. CONCLUSIONS: Our results suggest that hTERT protein expression and telomere shortening would be applicable as biological markers to distinguish FTC from FTA. Previous studies have suggested that follicular tumor and Hürthle cell tumor should be classified biologically as distinct tumors. All Hürthle cell tumors expressed hTERT protein and HCCs had markedly shortened telomeres, suggesting that follicular tumor and Hürthle cell tumor might be biologically distinct entities.

Therapeutic strategy for low-risk thyroid cancer in Kanaji Thyroid Hospital.

It is well-known that differentiated thyroid carcinoma (DTC) has a generally indolent character and shows a favorable prognosis in comparison with many other carcinomas. The therapeutic strategy for patients with DTC in Japan has differed from that in Western countries. Total thyroidectomy followed by radioactive iodine (RAI) ablation has been standard in Western countries, whereas limited hemi-thyroidectomy and subtotal thyroidectomy has been extensively accepted in Japan. Papillary thyroid carcinoma (PTC) accounts for over 90% of all thyroid cancers in Japan. The majority of patients with PTC are categorized into a low-risk group on the basis of the recent risk-group classification schemes, and they show excellent outcomes. Several management guidelines for thyroid cancers have been published in Western countries. However, the optimal therapeutic options for PTC remain controversial, and high-level clinical evidence aimed at resolving these issues is lacking. Moreover, as socioeconomic differences in medical care exist, conventional policies for the treatment of PTC have differed between Japan and other countries. This review focuses on the special features of treatment in Japan for patients with low-risk DTC involving subtotal thyroidectomy without adjuvant therapies, rather than total thyroidectomy with RAI, with the aim of preserving quality of life. At our institution in Japan, we have had extensive experience with RAI treatment for high-risk DTC patients, and this represents a very rare situation. Here we introduce the therapeutic strategy for low-risk thyroid cancer in Japan, including the measures adopted at our institution.

Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is less well recognized in Asian countries, including Japan, than in the West. The clinical features and optimal management of MEN1 have yet to be clarified in Japan. The aim of this study was to clarify the clinical features of Japanese patients with MEN1. DESIGN/PATIENTS: We established a MEN study group designated the 'MEN Consortium of Japan' in 2008, and asked physicians and surgeons to provide clinical and genetic information on patients they had treated. Of 680 registered patients, 560 were analysed. MEASUREMENTS: Clinical and genetic features of Japanese patients with MEN1 were examined. RESULTS: Primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumours (GEPNET), and pituitary tumours were seen in 94·4%, 58·6% and 49·6% of patients, respectively. The prevalence of insulinoma was higher in the Japanese than in the West (22%vs 10%). In addition, 37% of patients with thymic carcinoids were women, while most were men in western countries. The MEN1 mutation positive rate was 91·7% in familial cases and only 49·3% in sporadic cases. Eight novel mutations were identified. Despite the availability of genetic testing for MEN1, the application of genetic testing, especially presymptomatic diagnosis for at-risk family members appeared to be insufficient. CONCLUSIONS: We established the first extensive database for Asian patients with MEN1. Although the clinical features of Japanese patients were similar to those in western countries, there were several characteristic differences between them.

Localization of Ectopic Mediastinal Parathyroid Adenomas Using Indigo Carmine Injection for Surgical Management: A Preliminary Report.

An ectopic parathyroid adenoma (EPA) is a rare entity. The aim of this study was to report our experience in the preoperative localization and surgical management of EPAs. This was a multicenter retrospective study involving patients diagnosed with an EPA (three males and seven females) from January 2005 to November 2021. The clinical features, preoperative management, and surgical procedures were analyzed. A cervical neck ultrasound was performed in all patients and showed a focus in eight patients. Cervicothoracic enhanced computed tomography was performed in all patients and showed a focus in nine patients. The 99mTc-MIBI scintigraphy was performed in eight patients and showed uptake in six of them. We performed a neck dissection and thoracotomy in one patient, a thoracoscopy in one patient, surgery with a focused approach in seven patients, four of whom were injected with indigo carmine blue, and surgery with a bilateral approach in one patient. 1 h following the parathyroidectomy, the parathyroid hormone (PTH) concentration was decreased to 40-80% of the baseline value. Establishing a preoperative diagnosis of an EPA is challenging for the surgeon, despite the progress in the morphologic assessment. An intraoperative PTH assay and injection of indigo carmine have been shown to be valuable tools in the appropriate surgical management of an EPA.

Utilization of three-dimensional computed tomography for papillary thyroid carcinoma arising in the thyroglossal duct remnant: report of a case.

This report presents a rare and interesting case of papillary thyroid carcinoma arising in a thyroglossal duct remnant (TDR) that was diagnosed by three-dimensional computed tomography (3DCT). The patient, a 61-year-old woman, presented with a painless mass in the anterior suprahyoid region that had gradually enlarged over a 2-year period. Three-dimensional CT successfully revealed the thyroglossal duct (TD) descending from the tumor to the isthmus of the thyroid. An ultrasonography-guided fine-needle aspiration biopsy of the tumor was positive for carcinoma. A total thyroidectomy was performed in addition to the Sistrunk procedure. The histological findings indicated papillary thyroid carcinoma arising in the TDR and thyroid papillary microcarcinoma in the left thyroid lobe. The patient underwent radioactive iodine ablation and thyroid suppression therapy. This is apparently the first reported case of papillary thyroid carcinoma arising in a TDR evaluated using 3DCT. Three-dimensional CT was able to clarify the relative locations of the tumor, TD, and thyroid in the present case, and visualization of the TD allowed a definitive preoperative diagnosis that would not otherwise have been possible using conventional imaging techniques. This case suggests that 3DCT may therefore play an important role in providing definitive information on patients with anterior neck masses that are difficult to diagnose.

Follicular carcinoma arising from the pyramidal lobe of the thyroid.

We present a rare case of follicular carcinoma arising from the pyramidal lobe of the thyroid in a 21-year-old woman. Radical resection of the thyroid isthmus was performed, followed by adjuvant hormonal therapy with levothyroxine. After 15 months of follow-up, the patient remains disease-free. Thyroid carcinoma in children and adolescents is rare, and also rarely arises in the pyramidal lobe. To our knowledge, this is the first report of this type of neoplasm arising from the thyroid pyramidal lobe. We are following up this case carefully, and if recurrence or metastasis or both occur, we plan to perform total thyroidectomy and ablation with (131)I. This case suggests the importance of the differential diagnosis of midline cervical masses and the management of this type of neoplasm in adolescents.

Case Report: 84-Month Disease-Free Survival after Surgery for Anaplastic Thyroid Carcinoma.

We present a rare case of a patient with anaplastic thyroid carcinoma (ATC) who survived for 87 months after surgery. The patient was a 71-year-old man who presented with a painful enlarged mass in the right side of his neck that rapidly enlarged over 2 months. He was diagnosed with T4a, stage IVA ATC with no distant metastasis and underwent total thyroidectomy with modified neck dissection. Although only radiation and radioactive iodine therapy were administered after surgery, he remained disease-free for 84 months. Bone metastasis occurred after 84 months, and he was treated with Lenvatinib, but he died from a decline in his general condition 3 months later. We suggest that surgery is effective for stage IVA ATC, but adjuvant therapy is necessary for long-term disease-free survival in this patient population.

Prognostic utility of fluorescence in situ hybridization for determining HER2 gene amplification in breast cancer.

An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.

Telomere length variations in 6 mucosal cell types of gastric tissue observed using a novel quantitative fluorescence in situ hybridization method.

We developed a novel method for evaluating telomere length in 6 cell types of noncancerous and cancerous mucosal tissues from 11 cases of gastric neoplasm using the quantitative fluorescence in situ hybridization method with telomere and centromere peptide nucleic acid probes. Our telomere length estimates were determined from the background-corrected telomere intensity divided by the background-corrected centromere intensity (telomere-to-centromere ratio). Our results indicated that telomere lengths in each of the cases studied were reduced in turn from fibroblasts to fundic gland cells, to glandular neck cells, and then to surface foveolar cells. However, the telomere lengths of intestinalized cells located among fundic glands were not always shorter than those of the other cell types, as reported previously by others. Helicobacter pylori infection was suggested to induce the telomere shortening seen in the fundic glands. Although the mean telomere lengths varied among the 8 gastric cancer cases, correlation of the telomere lengths with the Ki-67 labeling index was established after normalization with the fibroblast measurements. We conclude that our telomere-to-centromere ratio method can reliably estimate the telomere lengths of the 6 cell types in the gastric mucosa and clarifies the relationship between proliferative activity and the telomere length of cancer cells.

Preoperative evaluation of thyroid pathology in patients with primary hyperparathyroidism.

In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery.

Squamous cell carcinomas of the esophagus arise from a telomere-shortened epithelial field.

Critically shortened telomeres make chromosomes susceptible to the instability and widespread cytogenetic alterations that characterize most human cancers. We hypothesized that the very rapid cell proliferation observed in esophageal squamous cell carcinomas might accelerate telomere shortening and chromosomal instability associated with carcinogenesis. We used a number of telomere measurement techniques including quantitative fluorescence in situ hybridization (Q-FISH) to compare chromosomal aberrations and telomere lengths of individual chromosomes in esophageal squamous cell carcinomas (ESCCs) and nearby non-neoplastic esophageal epithelium (NNEE) cells. Our results showed that the mean telomere length in ESCC cells was significantly less than that in adjacent NNEE cells, and that telomeres in all NNEE cells were significantly shorter than those in normal esophageal epithelium (reported previously). In addition, there was no evidence linking telomere shortening of a particular chromosome to field cancerization in ESCC. However, a mechanistic link between telomere shortening and chromosomal instability was supported by a higher frequency of anaphase/telophase bridges and an increase in the frequency of aneuploidy. This study furthers our understanding of the mechanism by which telomere shortening and chromosomal instability lead to carcinogenesis and field cancerization in the esophagus.

Telomere metabolism and diagnostic demonstration of telomere measurement in the human esophagus for distinguishing benign from malignant tissue by tissue quantitative fluorescence in situ hybridization.

OBJECTIVE: We have developed a novel method for evaluating telomere length in four different cell types in non-cancerous and cancerous mucosal tissue from 15 cases of squamous cell carcinoma of the esophagus using tissue quantitative fluorescence in situ hybridization (Q-FISH). We hypothesized that the very rapid cell proliferation observed in esophageal squamous cell carcinomas might accelerate the telomere shortening and chromosomal instability associated with carcinogenesis. METHODS: Tissue Q-FISH and the telomere to centromere intensity ratio (TCR) were used to compare telomere shortening in tissue sections taken from esophageal squamous cell carcinomas and adjacent non-cancerous esophageal tissues. RESULTS: The peak percentage of TCR was <1 for esophageal squamous carcinoma cells and >1 for the non-cancerous esophageal cell types. Basal layer cells had the longest telomeres in comparison with prickle, cancer, and stromal cells, and strongly expressed hTERT, cytokeratin 14 and CD49f, but not MIB-1. CONCLUSION: These results suggest the presence of stem cells in the basal layer of the esophagus. Esophageal squamous cell carcinomas also display anaphase bridges, evidencing chromosomal instability. In conclusion, our TCR method can be used to distinguish between benign and malignant tissue in esophageal lesions. In order to apply this approach clinically to individual cases, further studies are in progress.

Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer cell line OCUT-1.

One of the most aggressive human malignancies, anaplastic thyroid carcinoma (ATC), has an extremely poor prognosis that may be explained by its genomic instability. We hypothesized that the very rapid cell turnover observed in ATC might accelerate telomere shortening and chromosomal instability associated with tumor cell malignancy. To compare and measure chromosomal aberrations and telomere shortening in the anaplastic thyroid cancer cell line OCUT-1, we applied quantitative fluorescence in situ hybridization (Q-FISH) techniques. In all 15 metaphases studied, telomere length estimates from Q-FISH of chromosomes in ATC were shorter than those of a fibroblast cell line derived from the stroma adjacent to the carcinoma. OCUT-1 cells display several chromosomal abnormalities, but have a near-normal chromosome complement of 46, XX, making it easy to analyze the karyotype. The karyotype showed 50, XX, +7, +11, der(11)t(3;11)(q23;q23)x2, del(12)(p11.2p12), +20, +1mar. We analyzed carefully the abnormalities in karyotype of OCUT-1 associated with telomere shortening on each chromosome and expression of subtelomeres. Telomere lengths in the q-arms of the abnormal chromosome del(12)(p11.2p12) were shorter than the average length in the q-arms of the normal chromosome 12 in OCUT-1. Subtelomeres on the abnormal chromosome der(11)t(3;11)(q23;q23)x2 also showed loss of signals on 11p, but there was no loss of signals in the cytogenetically normal trisomies 7 and 20 or the abnormal chromosome del(12)(p11.2p12). Subtelomeres of 3q had eight signals, one pair remaining in place on 3q and another pair on the abnormal 11p. Our findings suggest that telomere shortening and subtelomere loss are correlated with genetic instability in this anaplastic thyroid carcinoma cell line.

The pathological findings of vasculitis simultaneously occurring with carcinoma, invasive breast carcinoma in a patient with Behçet's disease.

We present a rare case of invasive right breast carcinoma in a 72-year-old woman with Behçet's disease (BD). A radical modified right mastectomy and axillary lymphadenectomy were performed and postoperative hormonal therapy with the aromatase inhibitor anastrozole was administered for adjuvant therapy. At 10 months follow-up the patient remains disease free. Malignancies associated with BD are very uncommon. The pathological findings showed small vessel vasculitis and lobulitis of the breast in association with invasive carcinoma.

The Safety and Efficacy of Weekly Paclitaxel Administration for Anaplastic Thyroid Cancer Patients: A Nationwide Prospective Study.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive malignancy, with a median survival of less than 6 months due to rapid progression and resistance to multimodal therapies. Effective treatment strategies have not been identified. A prospective clinical study was performed to objectively evaluate outcomes of treatment with paclitaxel. METHODS: An investigator-initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate the feasibility and efficacy of weekly paclitaxel (80 mg/m(2)) administration for patients with pathologically confirmed ATC was conducted in a nationwide organization. RESULTS: Feasibility was analyzed in 56 patients. More than one course of treatment was performed in 52 (93%) patients retaining sufficient dose intensity (>84%). No patient had to terminate the treatment because of an adverse event. The median overall survival was 6.7 months [confidence interval 4.4-9.0]. The 6-month survival was 54%. Among the 42 patients with an evaluable lesion, none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%) achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not complete the initial treatment course. The objective response rate was 21%, and the clinical benefit rate was 73%. The median time to progression was 1.6 months. Statistically, no additional effect of concomitant radiation was demonstrated in 6 patients receiving combined therapy. Eight patients, in whom a complete post-treatment surgical removal of the tumor was feasible, survived significantly longer (median 7.6 months [CI 8.1-23.0]) than the other 34 patients in whom the tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0-7.8], p = 0.018). SUMMARY: The study demonstrates objective and accurate information concerning the feasibility and efficacy of a standardized treatment with weekly paclitaxel administration for ATC patients. CONCLUSIONS: Weekly paclitaxel administration for ATC patients can be of clinical benefit in a neo-adjuvant setting.

Ciliated surface in the esophagogastric junction zone: a precursor of Barrett's mucosa or ciliated pseudostratified metaplasia?

We have previously reported squamous metaplasia-like change at the esophagogastric junction (EGJ). In the present study, we examined these lesions histologically and by immunohistochemistry and electron microscopy. Samples of EGJ mucosa, 3 cm long and comprising 1.5-cm long portions of both columnar and squamous mucosa, were obtained from 43 esophagectomy resection specimens. Squamous metaplasia-like change was observed in 21 (49%) of the 43 cases. The squamous metaplasia-like change was generally positive with immunohistochemical stains for tubulin and cytokeratins (CKs) 4, 7, 8, 13, and 18, and was generally negative with stains for CKs 10, 14, and 20. This pattern of immunoreactivity is very similar to that of bronchial mucosa. Also, many cilia were detected at the apices of the cells by electron microscopy in 5 (31%) of the 16 cases that were able to be examined. Therefore, squamous metaplasia-like change at the EGJ has both a similar appearance and a similar immunohistochemical profile to respiratory bronchial epithelium. These findings may suggest that squamous metaplasia-like change at the EGJ is not a precursor of Barrett's mucosa but rather is a form of pseudostratified metaplasia.

Expression of human telomerase reverse transcriptase gene and protein, and of estrogen and progesterone receptors, in breast tumors: preliminary data from neo-adjuvant chemotherapy.

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is very closely associated with telomerase activity. Telomerase has been implicated in cellular immortalization and carcinogenesis. In situ detection of hTERT will aid in determining the localization of telomerase-positive cells. The aim of this study was to detect expression of hTERT mRNA, hTERT protein, estrogen receptor (ER) and progesterone receptor (PR) in paraffin-embedded breast tissue samples and to investigate the relationship between hTERT expression and various clinicopathological parameters in breast tumorigenesis. We used in situ hybridization (ISH) to examine hTERT gene expression, and immunohistochemistry (IHC) to examine expression of hTERT protein, ER and PR, in breast tissues including 64 adenocarcinomas, 2 phyllode tumors and their adjacent normal breast tissues. hTERT gene expression was detected by ISH in 56 (88%) carcinomas, but in neither of the 2 phyllode tumors. hTERT protein expression was detected by IHC in 52 (81%) carcinomas, but in neither of the 2 phyllode tumors. Moreover, ER and PR were expressed in 42 (66%) and 42 (66%) carcinomas, respectively, and in neither of the 2 phyllode tumors. In 4 cases of breast carcinoma that strongly expressed hTERT gene and protein before treatment, neo-adjuvant chemotherapy led to disappearance of gene and protein expression in all cases. There was a strong correlation between detection of hTERT gene expression by ISH and of hTERT protein by ICH in tissue specimens from breast tumors. These results suggest that detection of hTERT protein by ICH can be used to distinguish breast cancers as a potential diagnostic and therapeutic marker.