Investigation of the Subcellular Localization-Dependent Anti- or Pro-Tumor Functions of Maspin in Human Lung Adenocarcinoma Cell Line

Background: Mammary serine protease inhibitor (maspin) is well known as a tumor suppressor gene in several types of cancers and its nuclear localization is essential for its tumor-suppressive function. We previously reported that the cytoplasmic-only localization of maspin is significantly correlated with unfavorable prognosis in patients with lung adenocarcinoma (LUAD). To clarify whether maspin in LUAD acts as a tumor promoter or suppressor, we examined the subcellular localization-dependent biological functions of maspin in human LUAD cell lines. Methods: The expression levels and subcellular localization of maspin were investigated by performing immunoblotting and immunofluorescence in human LUAD cell lines (PC-9, A549, NCI-H23, RERF-LCKJ) and human bronchial epithelial cell line (BEAS-2B). We then established stable cell lines overexpressing maspin (A549-maspin and RERF-LC-KJ-maspin) and investigated their subcellular localization. Cell invasion assays of these cell lines were performed to examine their invasiveness. Moreover, the mRNA expression levels between epithelial cell markers (E-cadherin) and mesenchymal cell markers (N-cadherin and vimentin) were compared. Results: The expression of maspin in PC-9 cells was comparable to that in BEAS-2B cells, whereas its expression in A549, NCI-H23, and RERF-LC-KJ cells was decreased. The cell invasion capability of A549-maspin cells showing pancellular expression was significantly decreased compared with that of A549-control cells. By contrast, the cell invasion capability of RERF-LC-KJmaspin cells showing cytoplasmic-only expression was significantly increased compared with that of RERFLC-KJ-control cells. The mRNA expression levels of N-cadherin, but not E-cadherin and vimentin, in A549-maspin cells was significantly downregulated compared with that in A549-control cells. No significant differences in these markers were observed between RERFLC-KJ-maspin and RERF-LC-KJ-control cells. Conclusion: The invasive capability of LUAD cells is regulated by the intracellular localization of maspin. Clarification of the molecular mechanism underlying the subcellular localization-dependent function of maspin will promote a deeper understanding of LUAD development and progression

Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report

A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 × 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 × 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum

Maspin expression is frequent and correlates with basal markers in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Maspin is a unique member of the serine protease inhibitor superfamily and its expression is found in myoepithelial cells of normal mammary glands; therefore, it has been considered to be a myoepithelial marker. We previously reported that maspin was frequently expressed in biologically aggressive breast cancers. In turn, triple-negative (TN) breast cancer is a subtype of tumor with aggressive clinical behavior and shows frequent expression of basal markers. We hypothesized that maspin expression may be frequent and correlate with basal rather than myoepithelial markers in TN breast cancer.</p> <p>Methods</p> <p>Paraffin-embedded 135 TN invasive ductal carcinoma tissue samples were immunohistochemically investigated using the Dako Envision+ kit and primary antibodies for maspin, basal (CK5/6, EGFR, CK14) and myoepithelial markers (p63, CD10). The correlation between maspin expression and relapse-free survival (RFS) was investigated by the log-rank test.</p> <p>Results</p> <p>The positive rate for maspin was 85.9% and significantly correlated with younger age (<it>P </it>= 0.0015), higher histological grade (<it>P </it>= 0.0013), CK5/6 positivity (<it>P </it>< 0.0001), CK14 positivity (<it>P </it>= 0.0034) and the basal-like subtype defined by CK5/6, EGFR and CK14 positivity (<it>P </it>= 0.013). The positive rates for CK5/6, EGFR, CK14, CD10 and p63 were 59.2%, 48.9%, 34.1%, 17.8% and 12.6%, respectively. There was no significant correlation between maspin expression and RFS.</p> <p>Conclusions</p> <p>The positive rate for maspin is the highest among known basal and myoepithelial markers, and strongly correlates with basal markers in TN breast cancer. These results suggested that maspin could be a candidate for a therapeutic target for TN breast cancer.</p

Mucocele-like lesions of the breast: a long-term follow-up study

<p>Abstract</p> <p>Background</p> <p>Mucocele-like lesions (MLL) of the breast were originally described as benign lesions composed of multiple cysts lined by uniform flat to cuboidal epithelium with extravasated mucin, but subsequent reports described the coexistence of columnar cell lesions (CCL), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Several reports have investigated whether core biopsy can diagnose MLL reliably; however, there is only one report with a long-term follow-up after excision of MLL. We report here 15 surgically excised MLL with a long-term follow-up.</p> <p>Findings</p> <p>Fifteen lesions diagnosed as MLL from 13 patients who had undergone excisional biopsy between January 2001 and December 2006 were retrieved and followed-up for 24-99 months (median 63.8). Two lesions were accompanied with CCL, 5 with ADH and 3 with low grade DCIS. Four lesions (2 ADH, 2 DCIS) were additionally resected and their histology revealed 2 ADH, one DCIS and one MLL with CCL. Of 4 lesions (3 ADH, one DCIS) without additional resection, one lesion (ADH) relapsed accompanied with DCIS at 37 months after excision.</p> <p>Conclusions</p> <p>MLL were frequently accompanied with CCL, ADH or low grade DCIS. Complete resection may be recommended in case of MLL with ADH or DCIS because of intralesional heterogeneity and the probabilities of relapse.</p

Carcinosarcoma of Stomach Confined to the Mucosa

Carcinosarcoma is a malignant tumor composed of both epithelial and mesenchymal malignant tumor components. A 78-year-old man was transferred to our hospital because of hematemesis and tarry stool. An emergency gastrointestinal endoscopic examination revealed active bleeding from an ulcerative lesion on the posterior wall of the gastric body; endoscopic hemostasis was successfully performed. A gastrointestinal endoscopy performed two months later showed a polypoid lesion at the same place where the ulcer had been. The biopsy specimen was histologically diagnosed as well to moderately differentiated tubular adenocarcinoma. The patient underwent a laparoscopic distal gastrectomy with D2 lymph node dissection under a diagnosis of gastric adenocarcinoma. A 28 × 15 mm polypoid tumor was resected from the gastric body, and was found on microscopic examination to consist of both carcinoma and sarcoma components, showing atypical spindle cells, which were positive for α-smooth muscular actin, calponin, and h-caldesmon, but negative for CD34, CD117 (c-kit), desmin, and dog 1. These findings led to a diagnosis of gastric carcinosarcoma. The tumor was confined to the mucous membrane. Lymph node metastasis was found in one node and contained only the carcinoma component. The postoperative course was uneventful. The patient lived without recurrence for 2 years. Carcinosarcoma of the stomach is a rare tumor with high malignant potential and poor prognosis. Careful follow up is required for early detection of any recurrence

Clinical Significance of Subcellular Localization of Maspin in Breast Carcinoma: An Immunohistochemical Study Using Two Different Antibodies

Background: Maspin is known to be a tumor suppressor protein: however, its prognostic value in patients with breast cancer remains controversial. The key influential factors contributing to this complexity may be the differences in antibodies used, as well as the positive criteria and sample size. To date, no study has investigated the prognostic significance of maspin expression by using two different antibodies in the same cohort. We aimed to clarify whether differences in antibodies could influence on the prognostic value of maspin in breast cancer patients. Methods: Immunohistochemical analyses using an anti-maspin antibody (clone G167-70) were performed on 164 resected specimens of invasive carcinoma of no special type (NOS). The correlation with clinicopathological factors was compared to previous results using clone EAW24, with longer follow-up duration. Results: The subcellular localization of maspin expression was as follows: cytoplasmic-only staining, 3 cases (1.8%), pancellular staining, 43 cases (26.2%); and no staining, 118 cases (72.0%). No nuclear-only staining was observed. There was no significant correlation between clinicopathological characteristics and the pancellualr expression of maspin. The pancellular expression group showed a significantly longer disease-free survival (DFS) than the other groups (P = 0.046). When clone EAW24 was used, the cytoplasmic-only staining group showed significantly shorter DFS than the pancellular staining group (P = 0.003). Conclusion: Clone EAW24 may be superior to clone G167-70 in selecting breast carcinoma with an aggressive phenotype, while clone G167-70 may be superior to clone EAW24 in selecting non-aggressive breast carcinoma