Global methylation levels in peripheral blood leukocyte DNA by LUMA and breast cancer: a case-control study in Japanese women.

BACKGROUND: Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women. METHODS: We conducted a hospital-based case-control study of 384 patients aged 20-74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model. RESULTS: Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20-2.91) and 2.86 (95% CI=1.85-4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05). INTERPRETATION: These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk.

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer.

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05). It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion.

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

The likely transformation of papillary thyroid carcinoma into anaplastic carcinoma during postoperative radioactive iodine-131 therapy: report of a case.

We report herein a case of papillary carcinoma which appeared to transform into anaplastic carcinoma during postoperative radioactive iodine-131 (131I) therapy. A 67-year-old man who was diagnosed as having papillary thyroid carcinoma with bilateral neck lymph node involvement and multiple lung metastases underwent total thyroidectomy prior to 131I therapy. Immediately after a second course of 131I therapy, the patient complained of right neck pain and swelling, and a biopsy of the swollen neck lymph node was taken. Histologic examination of this biopsy specimen revealed anaplastic carcinoma. With p53 immunohistochemical staining, both the primary tumor and the biopsy specimen were positive. We speculate that first, some DNA damage in tumor cells was induced by the initial 131I therapy, but neither DNA repair nor cell apoptosis occurred because the p53 gene was already mutated; then further DNA damage was induced by the second 131I therapy, leading to anaplastic transformation.

[A case of painful tic convulsif due to cerebellopontine angle epidermoid tumor which could not be clearly detected by MRI].

A case of painful tic convulsif (trigeminal neuralgia and ipsilateral hemifacial spasm) caused by cerebellopontine angle epidermoid tumor is presented. This tumor was compressed to the trigeminal nerve, and became attached to the facial and auditory nerves. The facial nerve exit-zone of brain stem was also compressed by the tumor along with a branch of the posterior inferior cerebellar artery. Total removal of the tumor was carried out and neuralgia and facial spasm disappeared. Painful tic convulsif caused by brain tumor is rare (eight cases in the literature plus our case), but epidermoid tumor is not rare as a cause of this complaint (seven in eight cases). In preoperative examination of this case, we could not detect this epidermoid in the cerebellopontine angle, because this tumor was the same intensity as CSF liquid on magnetic resonance imaging (T1 and T2 weighted image) and exerting hardly any mass effect on the brainstem. On encountering a case of painful tic convulsif of unknown origin despite the usual preoperative examinations, it may be useful that same kind of brain tumor, especially, epidermoid might be concealed in the cerebellopontine angle lesion.