Kuniko Abe

RET/PTC Rearrangements Preferentially Occurred in Papillary Thyroid Cancer among Atomic Bomb Survivors Exposed to High Radiation Dose

A major early event in papillary thyroid carcinogenesis is constitutive activation of the mitogen-activated protein kinase signaling pathway caused by alterations of a single gene, typically rearrangements of the RET and NTRK1 genes or point mutations in the BRAF and RAS genes. In childhood papillary thyroid cancer, regardless of history of radiation exposure, RET/PTC rearrangements are a major event. Conversely, in adult-onset papillary thyroid cancer among the general population, the most common molecular event is BRAF(V600E) point mutation, not RET/PTC rearrangements. To clarify which gene alteration, chromosome aberration, or point mutation preferentially occurs in radiation-associated adult-onset papillary thyroid cancer, we have performed molecular analyses on RET/PTC rearrangements and BRAF(V600E) mutation in 71 papillary thyroid cancer cases among atomic bomb survivors (including 21 cases not exposed to atomic bomb radiation), in relation to radiation dose as well as time elapsed since atomic bomb radiation exposure. RET/PTC rearrangements showed significantly increased frequency with increased radiation dose (P(trend) = 0.002). In contrast, BRAF(V600E) mutation was less frequent in cases exposed to higher radiation dose (P(trend) < 0.001). Papillary thyroid cancer subjects harboring RET/PTC rearrangements developed this cancer earlier than did cases with BRAF(V600E) mutation (P = 0.03). These findings were confirmed by multivariate logistic regression analysis. These results suggest that RET/PTC rearrangements play an important role in radiation-associated thyroid carcinogenesis.

Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase π

Glutathione S‐transferase (GST) functions in xenobiotic biotransformation and drug metabolism. Increased expression of GSTπ, an isozyme of GST, has been found in cancer cells resistant to doxo‐rubicin hydrochloride (DOX) or cis‐diamminedichloro‐platinum (II) (CDDP), and this increase was believed to be correlated with drug resistance of cancer cells. GST is mainly expressed in the cytoplasm;GSTπ in the nucleus has been reported in cancer cells, but the meaning of this result is not known. Here, we studied changes in the amount of nuclear GSTπ after exposure of cancer cells to anticancer drugs, and role of the nuclear GSTπ in drug resistance. We found nuclear GSTπ in cancer cells resistant to DOX, and the amount of nuclear GSTπ was enhanced by treatment of the cancer cells with DOX or CDDP. We also found that a mushroom lectin, an inhibitor of nuclear transport, inhibited the nuclear transfer of GSTπ, suggesting the existence of a specific transport system for the nuclear transfer of GSTπ. Nuclear GSTπ protected DNA against damage by anticancer drugs. These results suggest a possible role of GSTπ in the acquisition of resistance to anticancer drugs by cancer cells.—Goto, S., Ihara, Y., Urata, Y., Izumi, S., Abe, K., Koji, T., Kondo, T. Doxorubicin‐induced DNA intercalation and scavenging by nuclear glutathione S‐transferase π. FASEB J. 15, 2702–2714 (2001)

Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis

There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression. Recently, it has been reported that angiopoietin-like 4 (ANGPTL4) expression in cancer cells promotes the metastatic process by increasing vascular permeability. The present study was conducted to examine ANGPTL4 expression and its association with clinicopathological factors and prognosis in human colorectal cancers. We examined 144 cases of surgically-resected human colorectal adenocarcinomas by immunohistochemistry, RT-PCR and Western blot analysis. Also, overall survival was investigated. Among 144 cases of adenocarcinoma, 95 cases (66.0%) showed positive staining in the cytoplasm of the carcinoma cells for ANGPTL4. Histologically, well, moderately, poorly differentiated adenocarcinoma or mucinous carcinoma showed 55.2, 79.3, 61.5 or 44.4% expression of ANGPTL4, respectively. The expression of ANGPTL4 was correlated with the depth of tumour invasion (p<0.0005), Vienna classification (category 3-5)(p<0.00005), venous invasion (p<0.0005) and Dukes classification (p<0.005). However, ANGPTL4 expression was not correlated with overall survival. However, all patients (100%) with distant metastasis showed immunopositivity for ANGPTL4. The mRNA and the protein expression of ANGPTL4 were shown in four resected samples and cultured cell lines by RT-PCR or western blot analysis. These findings suggest that ANGPTL4 is one of the factors involved in the progression of human colorectal cancer, especially venous invasion and distant metastasis.

Primary hepatic carcinoid tumor.

Abstract: A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 × 12 × 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.

Mass lesions surrounding coronary artery associated with immunoglobulin G4-related disease

Immunoglobulin G4 (IgG4)-related diseases have been reported to be systemic diseases characterized by elevation of serum IgG4 concentration and infiltration of IgG4-positive plasma cells within the target organ. However, the involvement of coronary artery is very rare. Here, we report a 62-year-old man with mass lesions surrounding coronary artery and abdominal aorta associated with IgG4-related disease diagnosed by a needle biopsy of the mass lesion surrounding the coronary artery using echocardiography and computed tomography. After we started to treat the patient with prednisolone, his serum IgG4 level decreased, and the mass lesions of coronary and abdominal artery were markedly reduced in size after 4 months. In conclusion, IgG4-related disease should be considered in addition to tumors such as malignant lymphoma when mass lesions surrounding coronary artery are detected.

A case of actinomycosis causing unilateral tonsillar hypertrophy

We report a case of unusual presentation of actinomycosis in the tonsil causing massive unilateral enlargement in a 78-year-old female. To our knowledge, only three cases of actinomycosis causing unilateral tonsillar enlargement have been published previously. Since this anaerobic organism is difficult to culture, the diagnosis is made by observing its associated sulfur granules in the biopsy specimen. In the present case, treatment consisting of tonsillectomy and antibiotic therapy (penicillin) for several days produced a good prognosis.

Mucosa-associated lymphoid tissue lymphoma of the thymus associated with Sjögren’s syndrome: Report of a case

A 68-year-old Japanese man with Sjögren’s syndrome was pointed out to have a nodular shadow in the anterior mediastinum. The tumor was resected under video-assisted thoracoscopy and it was pathologically diagnosed to be thymic mucosa-associated lymphoid tissue (MALT) lymphoma. There has been no recurrence for 17 months after surgery. Mucosa-associated lymphoid tissue lymphoma of the thymus is rare, and its pathological diagnosis requires sufficient knowledge and experience. Since thymic MALT lymphoma is distinct from MALT lymphoma of other sites in several ways, including gene abnormalities and geographic distribution, an alternative oncogenic pathway and the influence of racial and/or environmental factors must be considered to be involved. However, since the number of reported thymic MALT lymphomas is limited, these issues are still unclear. The accumulation of further similar cases will help to elucidate various issues concerning thymic MALT lymphoma associated with Sjögren’s syndrome.

Hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome: A case report

We report on a 3‐year‐old boy with circumferential skin creases as seen in Michelin tire baby syndrome (MTBS), hearing impairment, undescended testes, short stature, and mental handicap. Skin biopsy from the inguinal region showed degenerative collagen, which has never been found in MTBS. Similar clinical manifestations shared by our patient and a boy reported previously suggest a new clinical entity, in which degenerative collagen is etiologically involved. We propose an acronym to designate it: hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome.

Intraductal papillary growth of liver metastasis originating from colon carcinoma in the bile duct: Report of a case

Morphologically, liver metastases from colorectal carcinoma usually form as nodular tumor masses, whereas intraductal papillary growth in the bile duct is rare. A 65-year-old man underwent right hemicolectomy for advanced colon carcinoma, and histology of the primary carcinoma confirmed moderately differentiated adenocarcinoma with subserosal invasion, no vascular infiltration, and no lymph node metastasis. A liver tumor was found in the right paramedian Glisson pedicle and intraductal growth of cholangiocarcinoma was seen on imaging. We performed right hepatectomy and macroscopically, the resected specimen contained a growth in the bile duct lumen similar to cholangiocarcinoma. Histological examination revealed intraductal papillary proliferation of well-differentiated adenocarcinoma without vascular infiltration or lymph node metastasis in the hepatic hilum. Immunohistochemical staining revealed that the tumor cells were negative for cytokeratin-7 and positive for cytokeratin-20. Based on these findings, liver metastasis from colon carcinoma was diagnosed. Liver metastasis from colorectal carcinoma rarely arises as intraductal papillary growth in the bile duct, but the possibility of liver metastases with unusual morphology must be borne in mind for patients with a history of carcinoma in the digestive tract.

Diagnostic utility of diffusion-weighted magnetic resonance imaging in diabetic mastopathy

We report the clinical findings in a 36-year-old woman with diabetic mastopathy. The lesion showed heterogeneous segmental enhancement on magnetic resonance imaging (MRI), resembling a malignant lesion, but diffusion-weighted imaging (DWI) showed no abnormalities and the apparent diffusion coefficient value did not decrease. This case emphasizes the utility of DWI for differentiating diabetic mastopathy from malignant breast lesions. The value of DWI lies in its ability to exclude the possibility of malignant breast lesions and thus to avoid unnecessary biopsy.