A first Japanese Case of Intraductal Cancer of the Prostate with CHEK2 Mutation

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A first Japanese Case of Intraductal Cancer of the Prostate with CHEK2 Mutation

Background: Genomic profiling of tissue biopsies can be used to investigate genomic alterations. Although genomic analysis is also useful for precision medicine of prostate cancer, it is unclear whether to apply the results of this analysis to treatment. Case presentation: A 62-year-old man underwent docetaxel therapy and enzalutamide for castration-resistant prostate cancer. However, he developed urinary retention and radiological images showed progression of prostate cancer. We performed prostate biopsy and trans-urethral resection of the prostate. Pathological examination showed acinar adenocarcinoma with intraductal carcinoma. Although docetaxel rechallenge and cabazitaxel therapy were attempted, the tumor expanded to the rectum and his systemic condition worsened gradually (Fig. 1). Palliative care was started and the patient was transferred to another hospital. We performed next-generation sequencing using DNA from FFPE tissue of the TUR-P specimen. We identified 4 genetic variants with in the FFPE tissue sample. Remarkably, CHEK2 alteration was known to be associated with some solid cancer progression. Conclusions: The results of genetic analysis suggested that modification of tumor suppressor pathways might be associated with refractory nature of his cancer.

Ventral prostate and mammary gland phenotype in mice with complete deletion of the ERβ gene

Disagreements about the phenotype of estrogen receptor β (ERβ) knockout mouse, created by removing the DNA-binding domain of the ERβ gene or interruption of the gene with a neocassette (Oliver Smithies ERβ knockout mice [ERβOS−/−]), prompted us to create an ERβ knockout mouse by deleting the ERβ gene with the use of CRISPR/Cas9 technology. We confirmed that the ERβ gene was eliminated from the mouse genome and that no ERβ mRNA or protein was detectable in tissues of this mouse. Overall the phenotype of the ventral prostate (VP) and mammary gland (MG) in ERβcrispr−/−mice was similar to, but more severe than, that in the ERβOS−/−mice. In the VP of 6-mo-old ERβcrispr−/−mice there was epithelial hyperplasia, fibroplasia, inflammation, stromal overgrowth, and intraductal cancer-like lesions. This was accompanied by an increase in Ki67 and P63 and loss in DACH1 and PURα, two androgen receptor (AR) repressors. In the MG there was overexpression of estrogen receptor α and progesterone receptor, loss of collagen, increase in proliferation and expression of metalloproteases, and invasive epithelium. Surprisingly, by 18 mo of age, the number of hyperplastic foci was reduced, the ducts of the VP and MG became atrophic, and, in the VP, there was massive immune infiltration and massive desquamation of the luminal epithelial cells. These changes were coincident with reduced levels of androgens in males and estrogens in females. We conclude that ERβ is a tumor suppressor gene in the VP and MG where its loss increases the activity AR and ERα, respectively.

Positron Emission Mammography: High-Resolution Biochemical Breast Imaging

Positron emission mammography (PEM) provides images of biochemical activity in the breast with spatial resolution matching individual ducts (1.5 mm full-width at half-maximum). This spatial resolution, supported by count efficiency that results in high signal-to-noise ratio, allows confident visualization of intraductal as well as invasive breast cancers. Clinical trials with a full-breast PEM device have shown high clinical accuracy in characterizing lesions identified as suspicious on the basis of conventional imaging or physical examination (sensitivity 93%, specificity 83%, area under the ROC curve of 0.93), with high sensitivity preserved (91%) for intraductal cancers. Increased sensitivity did not come at a cost of reduced specificity. Considering that intraductal cancer represents more than 30% of reported cancers, and is the form of cancer with the highest probability of achieving surgical cure, it is likely that the use of PEM will complement anatomic imaging modalities in the areas of surgical planning, high-risk monitoring, and minimally invasive therapy. The quantitative nature of PET promises to assist researchers interested studying the response of putative cancer precursors ( e.g., atypical ductal hyperplasia) to candidate prevention agents.

Early Detection of Ductal Breast Cancer: The Diagnostic Procedure for Pathological Discharge from the Nipple

Pathologic discharge from the nipple may be the only symptom of an early stage of carcinoma. Galactography is then the diagnostic method of choice to locate intraductal, nonpalpable lesions. The technique of galactography, the adequate surgical approach of pathologic galactographs (milk-duct segment resection), and the appropriate histological work-up of the surgical specimen are demonstrated. We report on 1918 galactographies in 1363 women with pathological discharge. In only 427 cases was a milk duct segment resection necessary (31.4%). In 8.5%, we found invasive intraductal cancer and in 2.9% ductal carcinomata in situ. Only 1 patient with breast cancer had axillary metastases. Extensive intraductal solid, papillary or adenomatous proliferations were found in 11.9% of the patients with excision. In 46.7% of the patients, papillomas were excised, a definitive treatment for this process. The supposition for success in the early diagnosis of cancer is close teamwork among the radiology, surgery and pathology services: the diagnostic result depends upon this. We attribute our yield of exact diagnosis to a very sophisticated histological work-up. We believe that this is necessary to avoid diagnostic failures.