Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se. METHODS: We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. RESULTS: Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. CONCLUSIONS: Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.

Aortic aneurysm and craniosynostosis in a family with Cantu syndrome.

Cantu syndrome is an autosomal dominant overgrowth syndrome associated with facial dysmorphism, congenital hypertrichosis, and cardiomegaly. Some affected individuals show bone undermodeling of variable severity. Recent investigations revealed that the disorder is caused by a mutation in ABCC9, encoding a regulatory SUR2 subunit of an ATP-sensitive potassium channel mainly expressed in cardiac and skeletal muscle as well as vascular smooth muscle. We report here on a Japanese family with this syndrome. An affected boy and his father had a novel missense mutation in ABCC9. Each patient had a coarse face and hypertrichosis. However, cardiomegaly was seen only in the boy, and macrosomia only in the father. Skeletal changes were not evident in either patient. Craniosynostosis in the boy and the development of aortic aneurysm in the father are previously undescribed associations with Cantu syndrome.

Well-differentiated endocrine cell carcinoma of ileum treated by laparoscopy-assisted surgery--a case report.

A 72-year-old woman presented at our hospital with a 1-year history of intermittent right lower abdominal pain. Colonoscopic examination revealed a submucosal tumor with a pitted surface in the terminal ileum. Histopathological diagnosis of the carcinoid tumor was made following biopsy. Blood serotonin and urine 5-hydroxy-indoleacetic acid levels were normal, and carcinoid syndrome was not detected. Enhanced abdominal computed tomography scan and 18F-fluorodeoxyglucose positron emission tomography failed to detect multiple lesions, lymph node swelling or distant metastasis. Laparoscopy-assisted ileocecal resection with lymph node dissection was performed. The resected specimen showed a submucosal tumor with a pitted surface 11 x 11 mm in size, located at the terminal ileum. Histopathological examination revealed a well-differentiated endocrine cell carcinoma with an invasion depth to the muscularis propria. Immunohistochemical analysis showed the tumor cells to be chromogranin A and CD56-positive. The patient had no sign of recurrence for 16 months.

Characteristic gene expression in stromal cells of gastric cancers among atomic-bomb survivors.

To elucidate the mechanism of radiation-induced cancers, molecular analysis of cancers in atomic-bomb survivors is important. In our study, we developed a custom oligonucleotide array of 208 genes. We analyzed gene expression profiles of gastric cancers (GCs) from atomic-bomb survivors and identified 9 genes with significantly lower expression in GCs from exposed patients than in GCs from nonexposed patients. Among these 9 genes, expression of versican and osteonectin was investigated in greater detail using immunohistochemistry in 116 GCs from 64 exposed and 52 nonexposed patients who developed GC after the bombing. In the Stage I/II GCs, the clinicopathologic, phenotypic and proliferative characteristics of GCs from exposed and nonexposed patients did not differ significantly; however, versican and osteonectin were expressed at much lower levels in the area of tumor-associated stroma of exposed patients than in nonexposed patients (p = 0.026 and p = 0.024, respectively). These results suggest that the characteristics of tumor-associated stromal cells differ between GCs from exposed and nonexposed patients.

Positive immunohistochemical staining of gammaH2AX is associated with tumor progression in gastric cancers from radiation-exposed patients.

To elucidate the mechanism of radiation-induced cancers, molecular analysis of cancers in atomic bomb (A-bomb) exposure is important. DNA double-strand breaks (DSBs) are thought to be caused by the deleterious effects of ionizing radiation, and gammaH2AX (serine 139 phosphorylated form of histone H2AX) is reported to be a significant marker for DSBs. In the present study, we performed immunohistochemical analysis of gammaH2AX in gastric cancers (GCs) from 66 exposed and 47 non-exposed patients who developed GC after the bombing. Of the 47 GCs from non-exposed patients, 6 (13%) cases showed nuclear positive staining for gammaH2AX, whereas of the 66 GCs from exposed patients, 20 (30%) cases were positive (P=0.0405). However, among stage I GC, there was no significant difference in gammaH2AX expression frequency between exposed patients and non-exposed patients. Among exposed patients, stage II-IV cases were more frequently positive for gammaH2AX than stage I cases (P=0.0197). Among GCs from non-exposed patients, gammaH2AX staining showed no significant association with Lauren's classification, depth of invasion, lymph node metastasis or TNM stage. These results suggest that the characteristics of tumor cells differ between GCs from exposed and non-exposed patients. DSBs may be involved in progression of GC in exposed patients.

Immunohistochemistry of p63 in primary and secondary vulvar Paget's disease.

Vulvar Paget's disease (VPD) is classified into primary and secondary types. Differentiation of these subsets in biopsy specimen is important for appropriate therapy. Expression profile of cytokeratin (CK) 7 and CK20, gross cystic disease fluid protein-15 and uroplakin III has been reported as a differentiation marker of primary and secondary VPD. To examine the role of p63 immunostaining in differential diagnosis between primary VPD and VPD secondary to urothelial carcinoma (VPD-UC), expression of p63 was examined in nine cases of VPD. Paget cells in seven cases of VPD without UC did not express p63. In two cases of VPD associated with UC, Paget cells and UC cells had identical CK expression profile. UC cells were positive for p63 in both cases. In one case, Paget cells were positive for p63 and examination of the resected specimen showed that VPD was secondary to UC. In another case, Paget cells were negative for p63 and this was diagnosed as primary VPD independent of UC. This indicates that p63 is absent in Paget cells in primary VPD and is therefore useful in differentiating primary VPD from VPD-UC.

[Prediction of response to primary systemic chemotherapy involving weekly paclitaxel followed by FEC 100 for advanced breast cancer].

To predict the response to primary systemic chemotherapy (PSC) involving weekly paclitaxel (PTX) followed by FEC100, we analyzed the therapeutic effects of PSC on 58 cases of stage II - III advanced breast cancer, 2 cases of PD, 4 cases of suspension due to adverse events, and 52 successful cases (89.7%). As for clinical effect, CR was observed in 12 cases (23.1%) and PR in 33 cases (63.5%) and for histological effects, grade 3 (pCR) was observed in 7 cases (13.5%) and grade 2 in 13 cases (25.0%). At the time of completion of 4 courses of PTX, SD was observed in 34 out of 52 cases, but the number of SD decreased to 28 cases on completion of 8 courses of PTX, to 19 cases on completion of 12 courses of PTX, and to 7 cases on completion of 4 courses of FEC. In examining the 7 cases of pCR in whom the histological effect was observed, 3 cases of SD were observed on completion of 4 courses of PTX and 2 cases on completion of 8 courses of PTX. Unless PD is observed during the course of PSC, continuation of therapy would be indicated because of the delayed response.

Telomerase expression in noncancerous bronchial epithelia is a possible marker of early development of lung cancer.

Centrally located lung cancers in smokers frequently associated with subsequent primary tumors. We evaluated the telomerase expression chronologically in noncancerous epithelia as a risk factor of susceptibility to lung cancer development. Telomerase protein expression was examined in situ by immunohistochemistry in 26 noncancerous bronchial epithelia adjacent to centrally located early-stage lung cancers in sequential 23 patients treated by photodynamic therapy or surgery among 206 patients who underwent autofluorescence bronchoscopy from 1997 to 2003. Among the 15 lesions in 12 patients treated by photodynamic therapy alone, 11 lesions achieved complete remission after photodynamic therapy, and none of their noncancerous bronchial epithelia was telomerase positive. On the contrary, in the remaining four lesions, either recurrence or secondary lung cancer developed adjacent to the successfully treated primary cancer within 26 months, and the telomerase protein expression in noncancerous epithelia was detected before the secondary cancer development (P < 0.001). The overall relationship of human telomerase reverse transcriptase positivity in noncancerous epithelia and subsequent lung cancer development, including patients treated by radiation or surgery, showed higher significance (P < 0.0001). Histologically "normal" bronchial epithelia in smokers may unphysiologically express telomerase as a field, and such epithelia are likely susceptible to develop lung cancer. We propose that ectopic expression of telomerase in bronchial epithelia may precede transformation in human lung cancer development and that detection of telomerase protein in noncancerous bronchial epithelia will become a useful marker detecting high-risk patients for lung cancer development.

Perivascular epithelioid cell tumor of the jejunum.

Certain HMB-45-positive epithelioid cell tumors have recently been categorized under a unified concept: perivascular epithelioid cell tumor (PEComa). In this report, we describe ajejunal PEComa arising in a 32-year-old woman without other tumors or stigmata of tuberous sclerosis. The tumor consisted of nests of epithelioid cells with clear to granular eosinophilic cytoplasm. The nests were separated by thin fibrovascular septa. The tumor cells were positive for HMB-45 and progesterone receptor, and negative for cytokeratin, epithelial membrane antigen, vimentin, desmin, alpha-smooth muscle actin and CD34. RT-PCR analysis failed to reveal fusion transcript ETW/ATF1, which is characteristic of clear cell sarcoma of the soft parts. She developed a recurrent tumor at the pelvic wall and the left ovary at 13 and 25 months after the first operation, respectively. Each tumor was resected surgically, and no additional therapy was performed. We think the tumor of this case is a malignant form of PEComa because of the clinical history of multiple recurrences and the size of the primary tumor. Our case underscores that to make a correct diagnosis, clinical information and immunohistochemical examination are essential.

Radiofrequency ablation of early breast cancer followed by delayed surgical resection--a promising alternative to breast-conserving surgery.

To examine the radiofrequency ablation (RFA) reliability in early breast cancer, we performed RFA followed by delayed surgical resection on 41 patients with invasive or non-invasive breast carcinoma less than 2 cm. MRI scans were obtained before ablation and resection. Excised specimens were examined pathologically by haematoxylin-eosin and nicotinamide adenine dinucleotide-diaphorase staining. 40 patients completed 1 RFA session, which was sufficient to achieve complete tumour cell death. Overall complete ablation rate was 87.8% (36/41). There were no treatment-related complications other than that of a superficial burn in 1 case. After RFA, the tumour was no longer enhanced on MRI in 25/26 (96.2%) cases. Residual cancer, which was suspected on MRI in 1 case, was confirmed pathologically. MRI could be an applicable modality to evaluate therapeutic effect. RFA could be an alternate local treatment option to breast-conserving surgery for early breast cancer.

Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma.

Signet-ring cell carcinoma (SRCC) is a unique subtype of adenocarcinoma that is characterized by abundant intracellular mucin accumulation and a crescent-shaped nucleus displaced toward one end of the cell. Identification of an SRCC's primary site is important for better planning of patient management because the treatment and prognosis differs markedly depending on the origin of the SRCC. In the present study, we analyzed the immunohistochemical characteristics of 94 cases of SRCC, including 21 cases of gastric SRCC, 16 of colorectal SRCC, 10 of breast SRCC, and 47 of pulmonary SRCC, with antibodies against Reg IV and claudin-18, which we previously identified as gastric cancer-related genes. We also tested known markers cytokeratin 7, cytokeratin 20, MUC2, MUC5AC, caudal-related homeobox gene 2 (CDX2), thyroid transcription factor-1, mammaglobin, gross cystic disease fluid protein 15, and estrogen receptor. All 21 cases of gastric SRCC and 16 cases of colorectal SRCC were positive for Reg IV, and the remaining SRCCs were negative. Eighteen of 21 (86%) gastric SRCCs and 6 of 16 (38%) colorectal SRCCs were positive for claudin-18, whereas another SRCCs were negative. In conclusion, Reg IV staining and claudin-18 staining can aid in diagnosis of gastrointestinal SRCC.

Pleomorphic adenoma with extensive adenoid cystic carcinoma-like cribriform areas of parotid gland.

We report an interesting case of pleomorphic adenoma (PA) with extensive adenoid cystic carcinoma (ACC)-like cribriform areas of parotid gland along with a discussion of the differential diagnosis. The patient was a 62-year-old-female who presented with a 5-month history of a slow-growing painless mass in the left preauricular region. Pathological examination of the excised mass revealed a well-encapsulated tumor consisting of typical PA areas and extensive ACC-like cribriform areas. The transition between both areas was frequently observed. There was no clinical or histological evidence of a longstanding PA, such as prominent hyalinization with dystrophic calcification. Immunohistochemically, the neoplastic myoepithelial cells of the PA areas showed frequent expression of vimentin and S-100 protein, along with occasional positivity for glial fibrillary acidic protein and alpha-smooth muscle actin. The immunoreactivity of the neoplastic myoepithelial/basal cells forming cribriform nests was essentially identical to that of the PA areas. The difference of immunoreactivity of the basal/myoepithelial cells between PA and ACC may have some discriminatory advantage. In addition, the low proliferative activity observed in the entire tumor suggested that the cribriform nests resembling ACC are also the component of PA.

Immature teratoma of the ovary with a minor rhabdomyosarcomatous component and fatal rhabdomyosarcomatous metastases: the first case in a child.

A case of ovarian immature teratoma with rhabdomyosarcomatous recurrence in a 6-year-old girl is described. The primary tumor consisted of a dermoid cyst and a solid nodule composed of mature and immature mesenchymal tissue. The most immature mesenchymal cells showed no distinctive differentiation except for focal rhabdomyoblastic differentiation. The primary tumor was diagnosed as immature teratoma, grade 2, stage IIa. Despite left oophorectomy and excision of uterine serosal implants, chemotherapy, and radiation, four intrapelvic recurrences developed within 3 years. Although the primary tumor contained only a few rhabdomyoblasts, the recurrent tumors became increasingly rhabdomyosarcomatous. The patient died of systemic disease 3 years after presentation. This case and previous reports indicate that the prognosis of patients with ovarian immature teratoma with rhabdomyosarcomatous recurrence is poor and similar to that of primary ovarian rhabdomyosarcoma.