Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

Prasad, Manju L.; Bárbácioru, Cátálin; Rawal, Yeshwant B.; Husein, Omar F.; Wen, Ping

doi:10.1038/modpathol.3800983

Cited by 45 publications

(40 citation statements)

References 25 publications

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“…Unfortunately, other immunostains, including S100 and bcl-2, have not consistently helped differentiate PLGA from either adenoid cystic carcinoma or pleomorphic adenoma [13,18,39]. p63, an immunohistochemical stain that highlights basal and myoepithelial differentiation, has never routinely been used to distinguish between PLGA, adenoid cystic carcinoma, and pleomorphic adenoma because all three lesions are frequently positive for this marker [23,25,26]. However, while pleomorphic adenomas and adenoid cystic carcinomas have proven myoepithelial differentiation consistent with this staining pattern, no true myoepithelial component has been identified in PLGAs [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

“…p63, an immunohistochemical stain that highlights basal and myoepithelial differentiation, has never routinely been used to distinguish between PLGA, adenoid cystic carcinoma, and pleomorphic adenoma because all three lesions are frequently positive for this marker [23,25,26]. However, while pleomorphic adenomas and adenoid cystic carcinomas have proven myoepithelial differentiation consistent with this staining pattern, no true myoepithelial component has been identified in PLGAs [21][22][23]. As such, the p63 staining in PLGAs appears likely to represent aberrant expression of the TAp63 isoform similar to that seen in lung adenocarcinomas, soft tissue tumors, and lymphomas, raising the possibility that a more myoepithelial-specific antibody may be able to distinguish these lesions.…”

Section: Discussionmentioning

confidence: 99%

“…p63 is an immunohistochemical marker that is normally expressed in the basal layer of stratified epithelium, myoepithelial cells, and neoplasms that derive from these epithelia [24]. However, p63 has proven surprisingly unhelpful in distinguishing between PLGA, adenoid cystic carcinoma, and pleomorphic adenoma, as it often shows strong and diffuse positivity in PLGA despite its lack of myoepithelial differentiation [23,25,26]. Similar aberrant p63 immunolabeling has been seen in lung adenocarcinomas, soft tissue neoplasms, and lymphomas [27][28][29][30].…”

Section: Introductionmentioning

confidence: 88%

“…A potential basis for differentiating these three lesions is the fact that pleomorphic adenomas and adenoid cystic carcinomas harbor a prominent myoepithelial component, while PLGAs show no compelling immunohistochemical or ultrastructural evidence of true myoepithelial differentiation [21][22][23]. p63 is an immunohistochemical marker that is normally expressed in the basal layer of stratified epithelium, myoepithelial cells, and neoplasms that derive from these epithelia [24].…”

Section: Introductionmentioning

confidence: 99%

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Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Rooper

Sharma

Bishop

2014

Head and Neck Pathol

103

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Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes DNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63?/p40-adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63?/p40-staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63?/p40? or p63-/p40-immunophenotypes. PLGA consistently exhibits a p63?/p40-immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Rooper

Sharma

Bishop

2014

Head and Neck Pathol

103

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“…More recently, studies of protein expression, including ours, have taken advantage of this method. 23,24 The hierarchical clustering detected the mutually exclusive pattern of CK7 and DPEP1 (Figure 2c). Therefore, a combination of CK7 and DPEP1 staining is expected to distinguish ovarian metastases of colorectal cancers from primary mucinous ovarian carcinomas very accurately.…”

Section: Diagnosis Of Ovarian Metastasismentioning

confidence: 98%

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

et al. 2011

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Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold;^25% expression, Po0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-a, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (Po0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis. Modern Pathology (2011) 24, 267-276; doi:10.1038/modpathol.2010; published online 12 November 2010 Keywords: differential diagnosis; dipeptidase 1(DPEP1); metastasis; mucinous adenocarcinoma; ovaryThe ovary is a common site of metastasis, 1 and in many cases, there is a known history of primary tumors outside the ovary. However, ovarian masses are sometimes found in patients with no known history of malignancy and the primary tumor is not diagnosed until some time later. The morphology of a metastatic tumor in the ovary can mimic a primary ovarian tumor by a so-called maturation phenomenon. 2 A majority of the tumors exhibit cystic pattern when they metastasize to the ovary, whereas primary tumor in the original site is not cystic at all. Furthermore, many metastatic mucinous adenocarcinomas, especially from digestive organ cancers, contain a mixture of mucinous epithelium with a range of atypia, resembling primary mucinous carcinomas or borderline tumors. Many metastatic mucinous carcinomas of the ovary have been and continue to be misdiagnosed as primary ovarian mucinous adenocarcinomas. 3

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Polymorphous Low-Grade Adenocarcinoma

Seethala

Johnson²,

Barnes³

et al. 2010

Arch Otolaryngol Head Neck Surg

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Diagnosis of PLGA remains a challenge. Extrapalatal carcinomas appear to behave in a more aggressive fashion than those of the palate, and cancer arising from the base of the tongue frequently metastasizes to the cervical lymph nodes, suggesting a role for neck dissection in these patients. Recurrent cancers show evidence of histologic progression, justifying an aggressive approach to achieving initial complete excision.

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Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

Cited by 45 publications

References 25 publications

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1

Polymorphous Low-Grade Adenocarcinoma

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