Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas.

Overexpression of the ubiquitous protein kinase, CK2α, has been reported in various human cancers. Here, we demonstrate that nuclear and nucleolar CK2α localization in invasive ductal carcinomas of the breast is a reliable predictor of poor prognosis. Cellular localization of CK2α in nuclei and nucleoli was analyzed immunohistochemically using surgical tissue blocks from 112 patients, who had undergone surgery without neoadjuvant chemotherapy. Clinical data collection and median follow-up period were for more than 5 y. In total, 93.8% of patients demonstrated elevated CK2α expression in nuclei and 36.6% of them displayed elevated expression predominantly in nucleoli. Clinicopathological malignancy was strongly correlated with elevated nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly worse (P = .0002) in patients with positive nucleolar CK2α staining. The 5-y survival rate decreased to a roughly 50% in nucleolar CK2α-positive patients of triple-negative (P = .0069) and p Stage 3 (P = .0073) groups. In contrast, no patients relapsed or died in the triple-negative group who exhibited a lack of nucleolar CK2α staining. Evaluation of nucleolar CK2α staining showed a high secondary index with a hazard ratio of 6.629 (P = .001), following lymph node metastasis with a hazard ratio of 14.30 (P = .0008). Multivariate analysis demonstrated that nucleolar CK2α is an independent factor for recurrence-free survival. Therefore, we propose that histochemical evaluation of nucleolar CK2α-positive staining may be a new and robust prognostic indicator for patients who need further treatment. Functional consequences of nucleolar CK2 dysfunction may be a starting point to facilitate development of novel treatments for invasive breast carcinoma.

The relationship between BRCA-associated breast cancer and age factors: an analysis of the Japanese HBOC consortium database.

BRCA1/2 pathogenic variant prevalence in Japanese breast cancer is unclear. Here, we analyzed BRCA1/2 pathogenic variant prevalence with a particular focus on age factors, using the Japanese HBOC consortium database. All registered subjects were Japanese individuals who underwent BRCA1/2 genetic testing from January 1996 to July 2017 according to the Japanese HBOC consortium database. Cases were extracted and analyzed for each evaluation item. Overall BRCA1 and BRCA2 pathogenic variant prevalence was 11.2% and 9.0% in the cohort of 2366 proband patients, respectively. The age at onset of breast cancer for patients with BRCA1/2 pathogenic variants was significantly lower than that for patients without a BRCA1/2 pathogenic variant. In both BRCA1/2 patients, ages at onset were not statistically significantly different between two subtype groups (ER-positive vs. TNBC). We analyzed the BRCA1/2 pathogenic variant prevalence among age groups in patients with no family history of breast or ovarian cancer. In the TNBC group, the rate of genetic variants was more frequent among younger patients. Our results demonstrated that early breast cancer onset is associated with a BRCA1/2 pathogenic variant in the Japanese population. Younger TNBC patients were more likely to have a BRCA1/2 pathogenic variant irrespective of a family history of breast or ovarian cancer.

[A Case of Simultaneous Recurrence of Colon Cancer at the Drain Placement and Anastomotic Sites Postoperatively].

A woman in her 70s presented to our hospital with abdominal pain and right lower abdominal mass. Colonoscopy revealed circumferential ascending colon cancer. She underwent right hemicolectomy, D3 lymphadenectomy, and ileocolonic functional end-to-end anastomosis. The tumorwas pathologically diagnosed as T4aN1M0, Stage Ⅲa. Nine months afterthe first surgery, tumor marker levels increased, and detailed examination yielded a diagnosis of isolated recurrence at the site of drain removal in the abdominal wall. The tumor was resected without exposure. Four months after the second surgery, the tumor recurred in the abdominal wall. Furthermore, colonoscopy revealed anastomotic recurrence. Both recurrent tumors at the anastomotic site and in the abdominal wall were resected. No more recurrence has been detected to date. In this case, a possible cause of recurrence is implantation of cancer cells. Sufficient consideration should be given to innovations in intraoperative maneuvers and surgical wound protection, among others.

A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes.

We report an extremely rare case of familial breast cancer with deleterious germline mutations in both BRCA1 and BRCA2 genes, of which, to date, no such case has been reported among Japanese breast/ovarian cancer patients. Genetic testing of the family members indicated that the same double heterozygosity for BRCA1 and BRCA2 genes was transmitted to the paternal cousin, and the same BRCA2 mutation to the younger sister with bilateral breast cancer, younger brother with stomach cancer, and proband's son and daughter without cancer. Immunohistochemical analysis of BRCA protein expression was performed using breast cancer tissues from the proband with double heterozygosity for BRCA1 and BRCA2 genes and from her sibling without BRCA1 mutation but with BRCA2 mutation. There was no staining of either BRCA in the proband and no staining of BRCA2 in the sibling.

Multiple metastatic malignant melanoma presenting intraluminal gallbladder bleeding.

We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.

Clinicopathological study of non-palpable familial breast cancer detected by screening mammography and diagnosed as DCIS.

BACKGROUND: Recent widespread use of screening mammography has led to increased detection rates of non-palpable breast cancer. This study aimed to evaluate the clinicopathological features of non-palpable ductal carcinomas in situ of the breast that were detected by screening mammography of patients with a family history of breast cancer. METHODS: We selected 6 Japanese patients diagnosed with non-palpable breast cancer with self-reported family history of breast cancer. Mutations in BRCA1 and BRCA2 were evaluated with germ line genetic testing and immunohistochemistry (IHC) using resected specimens. Pathological features, such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, were also evaluated. RESULTS: The patients (ages 41-67 years; mean 53.5) had 7 tumors with one patient having synchronous bilateral breast cancer. Breast cancer was suspected from the microcalcification in 5 tumors and the distortion in 2 tumors by mammography and diagnosed by biopsy. Breast-conserving surgery was performed in 2 patients and mastectomy was performed in 4 patients. Genetic testing revealed BRCA2 gene germ line mutation in three patients. IHC of BRCA was consistent with BRCA2 mutation status. CONCLUSIONS: The family history of breast cancer patients may lead one to suspect familial breast cancer and screening mammography is useful for the early detection of these cancers. IHC of BRCA showed staining results that were consistent with BRCA genetic testing, suggesting that it has the potential to be a useful tool in clinical practice.

[A case of triple-negative breast cancer achieved pCR by epirubicin and cyclophosphamide(EC)therapy followed by gemcitabine plus paclitaxel combination preoperative therapy].

A 59-year-old woman was diagnosed with triple-negative breast cancer(TNBC)(T2N0M0)and treated with primary systemic therapy. The patient was treated with 4 courses of epirubicin and cyclophosphamide(EC)therapy every 3 weeks, followed by weekly gemcitabine-paclitaxel combination therapy. As she was judged to have achieved a partial response(PR) by ultrasound and CT examination after eight courses, she underwent partial resection of the left breast. CR was revealed by the pathological examination of the resected specimen. Gemcitabine-paclitaxel combination therapy seems to be a one of the useful preoperative chemotherapies for TNBC.

Hemorrhagic cytomegalovirus colitis in a postoperative colon cancer patient.

We report a case of hemorrhagic cytomegalovirus (CMV) colitis, occurring in a postoperative patient due to a weakened immune system. An 85-year-old woman with a medical history, including chronic renal failure treated with oral administration of prednisolone, underwent colectomy due to an ascending colon cancer. While the postoperative course was favorable, she exhibited acute severe abdominal pain and massive bloody discharge after 11 days of surgery. Her colonoscopic examination showed multiple longitudinal ulcers on the anastomosis. In addition to these endoscopic findings, her past medical history helped suggest CMV colitis. Because serological testing revealed positive CMV antigen, she was finally given a diagnosis of CMV colitis and received intravenous ganciclovir for the initial treatment. Hemorrhagic CMV colitis after colectomy is an important postoperative complication; we therefore present our case with diagnosis and treatment experience.

[The clinical study of familial breast cancer - now and the problems].

The clinical features of familial breast cancer are characterized by early onset, high frequency of bilateral breast cancer, and multiple malignancies of other organs. It is strongly suggested that genetic factors contribute to familial breast cancer. The causative genes now identified are BRCA1 and BRCA2. This disease is called hereditary breast ovarian cancer syndrome (HBOC)because breast cancer and ovarian cancer are clustered in the kindred confirmed BRCA mutation. As for BRCA related breast cancer, early onset and highly frequent bilateral breast cancer are characteristic. In addition, the histological grade is high and the positive rate of estrogen receptors is low in BRCA1-related breast cancer. Gene diagnosis of BRCA is useful when choosing a surgical method, chemotherapy, or a surveillance of mutation carriers. The problem in Japan is that the treatment is very expensive, with poor understanding of HBOC of by clinicians and as yet immature genetic counseling system.

Three cases of kindred with familial breast cancer in which carrier detection by BRCA gene testing was performed on family members.

We performed presymptomatic carrier detection by BRCA gene testing of the family members of three familial breast cancer kindred diagnosed with pathogenetic mutation in BRCA genes. All members were over 20 years of age. We explained familial breast cancer and BRCA gene testing, and obtained autonomic consent before gene testing. Genetic testing revealed twins in a family were dizygotic. In another family bilateral breast cancer occurred in a carrier after five years of genetic testing. Carriers are at high risk of breast cancer and have to receive breast cancer screening and familial tumor counseling. Non-carriers are at the same risk of breast cancer as the general population.

A case of primary malignant lymphoma of the breast with an unusual ultrasound image.

The patient was a 50-year-old woman with a palpable tumor and pain in the right breast in May of 2008. The tumor was then diagnosed as an atheroma. The tumor enlarged rapidly in June, and the pain and the redness had worsened. The patient was then referred to our hospital. The tumor was in the upper inner quadrant of the right breast with surface redness, measuring about 3 cm. In the mammographic (MMG) findings, the tumor shadow was in the upper inner quadrant of the right breast and was observed to be circular and have a high density with a plain boundary and slightly roughed edges. In the ultrasonographic (US) findings, an oval-shaped high echoic region was found subcutaneously in the right breast. Because the high echoic area was subdivided in the partition of the low echoic string, it looked like a pebbled wall. Upon core needle biopsy, this case was diagnosed as malignant lymphoma. After comparing the histopathology and the US image, it was determined that the pebbled wall-shaped image was due to lymphocyte infiltration of the tissue. The US image was peculiar and we report this case as a peculiar example of malignant lymphoma.

Locally advanced and metastatic breast cancer with cartilaginous and/or osseous metaplasia showing excellent response to chemotherapy.

Breast cancer with cartilaginous and/or osseous metaplasia is considered a rare disease, but several cases have been reported recently. We report a case of breast cancer with cartilaginous and/or osseous metaplasia that was StageIV,(T4bN0M1b (PUL)), on the basis of the Japanese General Rules for Clinical and Pathological Recording of Breast Cancer, which responded well to chemotherapy. A 58-year-old women visited our hospital with a chief complaint of a palpable breast mass that had increased in size in March 2002. It was 20 x 15 x 14 cm and occupied the entire right breast. Chest computed tomography (CT) demonstrated multiple lung metastases. Histology of the biopsy specimens revealed a spindle-shaped cell carcinoma. It was ER(-), PgR(-), and HER2/neu Score 0. CAF was given to the patient as preoperative chemotherapy. Five cycles of treatment yielded improvement at the primary site and improvement of the metastatic lung lesions, which was judged as a partial response. Subsequently, one cycle of weekly paclitaxel 80 mg/m2 and oral administration of 5'-DFUR 800 mg/day were given. In November 2002, the patient underwent a right simple mastectomy with whole-layer skin grafting from the abdomen. The final pathological diagnosis was a rare type of breast cancer with cartilaginous and/or osseous metaplasia. Preoperative chemotherapy had caused necrosis in most of the tumor cells, and the efficacy was judged as Grade 2. From the third week postoperatively, weekly paclitaxel (80 mg/m2) was given. Six months after the operation, the multiple lung metastases were completely eliminated and new metastasis to liver or bone or local recurrence have not been observed.

A case of breast cancer metastasizing to cervix after resection of pancreatic metastasis.

A case of breast cancer that metastasized to the cervix 10 years and 8 months after mastectomy is reported. The patient had undergone pancreaticoduodenectomy due to solitary metastasis to the head of the pancreas 4 years previously. The cervical metastasis was associated with abnormal genital bleeding. After pancreaticoduodenectomy the serum levels of CEA, CA15-3 and NCC-ST-439, which are markers of breast cancer, were within normal limits, but the serum level of CA15-3 had increased month by month. The patient had abnormal genital bleeding and presented to the department of gynecology at our hospital. The tumor was in the cervix, bled easily and 2.5x2.0 cm in size on ultrasonography. It was thought to be carcinoma of the cervix, but biopsy revealed the tumor to be an adenocarcinoma pathologically and CA15-3 was immunohistochemically demonstrated in the resected specimen, similar to lobular carcinoma of the breast. Abdominal CT scan revealed involvement of the ovaries and uterus, prompting hysterectomy with bilateral oophorectomy. After discharge, she received chemoendocrine therapy. However, she subsequently died due to peritoneal carcinomatosis.