Diagnostic Utility of SATB2 in Metastatic Krukenberg Tumors of the Ovary: An Immunohistochemical Study of 70 Cases With Comparison to CDX2, CK7, CK20, Chromogranin, and Synaptophysin.

SATB2 is a sensitive marker for colorectal adenocarcinomas. No study has investigated its diagnostic utility in metastatic Krukenberg tumors (MKTs) of the ovary. Here we performed immunohistochemical staining SATB2 in 70 MKTs of various origins (stomach 27, colorectum 13, appendix 20 including 19 metastatic adenocarcinomas ex goblet cell carcinoids [AdexGCC] and 1 conventional poorly differentiated carcinoma with signet ring cells, breast 5, bladder 3, lung 2) to assess its diagnostic utility. We also compared SATB2 with CDX2, CK7, CK20, chromogranin, and synaptophysin in MKTs of gastric origin (MKTs-stomach), those of colorectal origin (MKTs-colorectum) and those due to appendiceal AdexGCCs (MKT-AdexGCCs) for their sensitivity and specificity to distinguish these tumors. SATB2 staining was seen in 1/27 (4%) MKTs-stomach (40% cells), 7/13 (54%) MKTs-colorectum (mean: 17% cells, median: 7%, range: 2% to 60%), and 19/19 (100%) of MKT-AdexGCCs (mean: 97% cells, median: 100%, range: 80% to 100%) (P<0.01 between any two). SATB2 staining was seen in 1/1 metastatic appendiceal poorly differentiated carcinoma with signet ring cells (5% cells), 1/3 MKTs of bladder origin (60% cells), 0/2 MKTs of pulmonary origin, and 1/5 MKTs of breast origin (10% cells). SATB2 staining was diffuse strong in MKT-AdexGCCs whereas in other MKTs it was focal and weak in the signet ring and nonsignet ring nonglandular cells and from focal weak to diffuse strong in well-formed glands. MKTs-stomach, MKTs-colorectum, and MKT-AdexGCCs showed no significant staining difference in CDX2 (100%, 100%, 100% cases, respectively; P=1.0), CK20 (96%, 100%, 100%, respectively; P=1.0), chromogranin (59%, 31%, 63%, respectively; P>0.05) or synaptophysin (59%, 63%, 84%, respectively; P>0.05) but they had significant difference in CK7 staining (93%, 8%, 42%, respectively; P<0.05). Among these 6 markers, SATB2 is the best one to distinguish MKT-AdexGCCs from MKTs-stomach (100% sensitivity, 96% specificity) and MKTs-colorectum (100% sensitivity and 100% specificity if staining more than 75% tumor cells as the cutoff). In distinguishing MKTs-stomach from MKTs-colorectum, SATB2 is not as good as CK7 which is the best marker. Our results indicate that SATB2 is a highly sensitive marker (100% sensitivity) for metastatic MKT-AdexGCCs with high specificity (100% specificity when showing strong staining in at least 75% cells) among MKTs. SATB2 is a useful marker for determining the primary sites of MKTs of the ovary.

Krukenberg tumor in a 18-year-old-female: a rare case.

BACKGROUND: Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare. CASE: A 18-year-old female presented with colon cancer which was accompanied by Krukenberg tumor. The present case was a very rare case of metastatic ovarian tumor in very young age. The present patient presented with abdominal pain. On examination, colon tumor was detected and bilateral ovary were almost normal with only slight swelling. During the operation for colon tumor, biopsy of bilateral ovary was performed for histopathological evaluation. Although there were no specific findings in bilateral ovary, microscopic examination revealed poorly differentiated adenocarcinoma, diffusely invading the ovarian parenchyma. Diagnosis of colon cancer was made postoperatively and ovarian Krukenberg tumor was confirmed. CONCLUSION: In case of suspecting colon cancer even in very young patient with normal ovary, biopsy of ovary should be considered for the diagnosis of Krukenberg tumor.

Diagnostic value of dual detection of hepatocyte nuclear factor 1 beta (HNF-1ß) and napsin A for diagnosing ovarian clear cell carcinoma.

We evaluated the diagnostic value of hepatocyte nuclear factor 1 beta (HNF-1ß) and napsin A for diagnosing ovarian clear cell carcinoma. Immunohistochemical EnVision was used to measure HNF-1ß and napsin A expression in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma, and 16 metastatic Krukenberg tumor cases. Then we found that HNF-1ß appeared in all ovarian clear cell carcinoma and was less common in high-grade serous and endometrioid adenocarcinoma (P < 0.05). However, no significant difference in HNF-1ß between clear cell carcinoma and metastatic Krukenberg tumor was found (P > 0.05). Napsin A was expressed in 97.4% of ovarian clear cell carcinoma, 6.7% high-grade serous carcinoma, 22.7% endometrioid adenocarcinoma, and 0% metastatic Krukenberg tumors. Napsin A in clear cell carcinoma was greater than that found in high-grade serous carcinoma, endometrioid adenocarcinoma, and metastatic Krukenberg tumor (P < 0.05). Sensitivity and specificity of HNF-1ß and napsin A for diagnosing ovarian clear cell carcinoma was 100% and 54.4%, and 97.4% and 89.7%, respectively. Sensitivity and specificity of HNF-1ß and napsin A for diagnosing ovarian clear cell carcinoma was 97.4% and 91.2%, respectively. So it is concluded that HNF-1ß and napsin A are more sensitive than currently used markers for diagnosing ovarian clear cell carcinoma. Moreover, napsin A is more specific than HNF-1ß. Combining HNF-1ß and napsin A may distinguish clear cell carcinoma from high-grade serous carcinoma, endometrioid adenocarcinoma and metastatic Krukenberg tumors.

Krukenberg carcinoma metastasized from stomach resembling mucinous cystadenocarcinoma of the ovary.

The ovaries are common site of metastasis in a variety of primary neoplasms. Multiple tumors such as breast, lung, and pancreas have been reported to metastasize to the ovary, however; the colon and stomach are the most common primary cancer sites that of ovarian metastasis. An ovarian mass mostly originates from its self-tissue, but sometimes it can be a metastasis of a gastrointestinal system tumor. Such cases are often misdiagnosed as primary ovarian cancers. A 42-year-old woman was admitted to our hospital with pelvic pain. She had a history of her complaints for two months. Bilateral large ovarian mass was detected in transvaginal ultrasound. Laparotomy was performed, the pathologist suggested inspection of the stomach after the frozen section analysis; therefore, an irregular mass on the stomach was detected. The general surgeon was attended to the operation, and an inoperative stomach tumor was reported by the general surgeon. After that due to the partial obstruction of jejunum, a gastrojejunostomy was performed. It is in fact difficult to distinguish between metastatic mucinous carcinomas and primary mucinous carcinomas of the ovary, due to the similar appearance of as cystic tumors on gross examination. The clinicians should be aware of the likely concomitant gastrointestinal system tumor when a large and bilaterally mass was detected on physical examination. This case also reminds that a systemic examination is necessary even if the large ovarian tumors suspicious of primary malignancy were noticed.

Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types.

In this study, 60 different types of ovarian lesions, mainly consisting of ovarian neoplasms, were studied for the expression of claudins 1, 4, 5, and 7. Strong expression of claudins 1, 4, and 7 was seen in benign and malignant epithelial ovarian tumors. Expression of claudin 5, reported to be mainly present in endothelial cells, was seen in ovarian epithelial tumors, but with a significantly lower frequency than claudins 1, 4, and 7. On the contrary, sex-cord stromal tumors and cysts, such as fibromas/thecomas, Sertoli-Leydig cell tumors, granulosa cell tumors, and follicular and luteinized cysts were mainly negative for claudins 1, 4, 5, and 7. Interestingly, adenomatoid tumors did not express claudin 5, which is in agreement with their non-endothelial nature. They were also negative for claudin 4, but expressed claudins 1 and 7, but to a lesser degree than epithelial lesions. In immature teratomas, the epithelial component was usually positive whereas other components were negative for these claudins. Dysgerminomas did not express any of the claudins studied. The results show that claudins 1, 4, and 7 are mainly expressed in ovarian epithelial tumors and can thus be used to indicate epithelial differentiation in them. Eventhough considered an endothelial marker, claudin 5 was also present in a subset of epithelial lesions. However, this claudin can be used to differentiate adenomatoid tumors from vascular lesions. No significant difference was seen between epithelial benign and malignant lesions, except for claudin 5, which seemed stronger in malignant epithelial tumors.

Krukenberg tumor of renal pelvic origin: report of a case with selected comments on ovarian tumors metastatic from the urinary tract.

Metastatic tumors to the ovary are infrequently of urinary tract origin. In approximate descending order of frequency, this subset of secondary ovarian neoplasms includes renal cell carcinoma, transitional cell carcinoma of the urinary bladder, and urachal adenocarcinomas. These tumors usually raise a differential in turn of primary ovarian clear cell, transitional cell, or mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the bladder have shown the features of a Krukenberg tumor. We report the case of a 74-year old woman with bilateral Krukenberg tumors metastatic from a primary renal pelvic transitional cell carcinoma with glandular and signet-ring cell differentiation. This unique case reinforces that tumors with signet-ring cell morphology have a propensity to metastasize to the ovary, and indicates that renal pelvic carcinoma rarely may be the source of Krukenberg tumors.

Beta-catenin expression in intramucosal neoplastic lesions of the stomach. Comparative analysis of adenoma/dysplasia, adenocarcinoma and signet-ring cell carcinoma.

OBJECTIVE: To clarify roles of beta-catenin in the early stage of gastric tumorigenesis, we investigate beta-catenin expression in stomach intramucosal neoplasms. METHODS: For immunohistochemistry, 84 gland-forming neoplasms and 17 signet-ring cell carcinomas were examined. The gland-forming neoplasms were grouped according to the Vienna classification: group A (low-grade adenoma/dysplasia), group B (high-grade adenoma/dysplasia) and group C (intramucosal carcinoma). RESULTS: Strong nuclear expression was detected not only in group C (21.4%) but in groups A (20.8%) and B (11.2%). Strong cytoplasmic expression was detected in groups A, B and C: 16.7, 11.2 and 16.7%, respectively. Loss of membranous stainings (LOM) were also detected in groups A, B and C: 20.8, 22.2 and 31.0%, respectively. No significant difference was found among groups A, B and C with respect to nuclear, cytoplasmic, and membranous expression. Regarding signet-ring cell carcinomas, all cases were essentially negative for nuclear expression and 11.8% of the cases showed weak cytoplasmic expression as well as LOM. There were obvious differences between gland-forming adenocarcinoma and signet-ring cell carcinoma with respect to nuclear and cytoplasmic expression but not in terms of membranous expression. CONCLUSION: These findings suggest that beta-catenin expression does not always reflect the malignant transformations in the early stage of gastric tumorigenesis.

Serum and tissue measurements of CA72-4 in ovarian cancer patients.

Serum levels of cancer-associated antigen 72-4 (CA72-4) (tumor-associated glycoprotein 72; TAG-72) from 106 patients with primary ovarian cancer were measured by an immunoradiometric assay employing the monoclonal antibodies (MAbs) B72.3 and CC49. Immunohistochemical localization of TAG-72 was also investigated using immunoperoxidase methodology in conjunction with both light and electron microscopy. In using a cutoff value of 4.0 U/ml for the serum assay, sensitivity of all primary ovarian carcinomas was 63.2% (67.6% of mucinous cystadenocarcinomas and 66.7% of serous cystadenocarcinomas), while specificity of benign ovarian tumors was 91.1%. Diagnostic characteristics of CA125 and CA72-4 have been demonstrated by receiver-operating-characteristics analysis. Although CA125 expressed a remarkable diagnostic efficiency with serous cystadenocarcinoma, it was less efficient with mucinous cystadenocarcinoma. CA72-4, however, was highly detectable for any histological type of ovarian cancer. Immunohistochemical staining with MAbs B72.3 and CC49 in the cytoplasm was stronger than that in the cell membrane in tissues from mucinous cystadenocarcinomas. Also, histological localization of TAG-72 in the microvilli and apical cytoplasmic membrane was demonstrated by electron microscopy using MAb B72.3 and samples of seromucinous cystadenocarcinoma (mixed type). Consequently, TAG-72 was useful for the detection of ovarian carcinoma, especially for monitoring mucinous cystadenocarcinoma, and it is localized in the microvilli and apical cytoplasmic membrane of cystadenocarcinoma cells.