Clinical Validation of Coexisting Activating Mutations Within EGFR, Mitogen-Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung Cancers.

Abstract:

CONTEXT.—:Mutations within the same signature transduction pathway are redundant and, therefore, most are mutually exclusive. Laboratory errors, however, may introduce unexpected coexisting mutations. OBJECTIVE.—:To validate coexisting mutations within epidermal growth factor receptor (EGFR), mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. DESIGN.—:In this retrospective study for quality assessment of next-generation sequencing in a clinical diagnostics setting, coexisting mutations within EGFR, KRAS, NRAS, BRAF, AKT1, and PIK3CA genes were examined in 1208 non-small cell lung cancers. RESULTS.—:EGFR mutations did not coexist with BRAF mutations, neither kinase-activated nor kinase-impaired mutations. There was a low but similar incidence (3.3%-5.1%) of PIK3CA mutations in BRAF-, EGFR-, and KRAS-mutated lung cancers and a rare incidence of coexisting KRAS and EGFR mutations detected in 1 of 1208 lung cancers (0.08%) or 1 of 226 EGFR-mutated lung cancers (0.4%). Coexisting BRAF p.V600E mutation was observed in 3 of 4 AKT1 p.E17K-mutated lung cancers. Mutational profiling of DNA reisolated from subareas with the same or different histomorphology, using an alternative assay, confirmed that coexisting mutations might present within the same (whole or subclonal) population or different populations and clarified that the so-called coexisting activating KRAS and BRAF mutations originally reported in a specimen were indeed present in separate lung nodules submitted in the same block. CONCLUSIONS.—:The results supported that EGFR and BRAF mutations are early driver mutations in lung cancers. Guidelines from official organizations to establish standard operating procedures are warranted to validate unexpected coexisting mutations and, if clinically indicated, to determine their presence in the same or different tumor populations.

journal_name

Arch Pathol Lab Med

authors

De Marchi F,Haley L,Fryer H,Ibrahim J,Beierl K,Zheng G,Gocke CD,Eshleman JR,Belchis D,Illei P,Lin MT

doi

10.5858/arpa.2017-0495-OA

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

174-182

issue

2

eissn

0003-9985

issn

1543-2165

journal_volume

143

pub_type

杂志文章
  • Sturge-Weber syndrome. A case with thyroid and choroid plexus hemangiomas and leptomeningeal melanosis.

    abstract::We studied a case of Sturge-Weber syndrome in a 66-year-old woman, who displayed associated angiomas of the thyroid gland and choroid plexi and leptomeningeal melanosis. These findings are discussed in light of the proposed pathogenesis of the syndrome and its relationship to the other neuroectodermal dysplasias. ...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Bentz MS,Towfighi J,Greenwood S,Zaino R

    更新日期:1982-02-01 00:00:00

  • Granulomatous encephalitis caused by Bipolaris hawaiiensis.

    abstract::We describe a case of granulomatous encephalitis caused by Bipolaris (Drechslera) hawaiiensis in an immunocompetent patient. An 18-year-old man with a seven-month history of seizures and right leg weakness was found by computed tomographic scan to have a left frontoparietal enhancing lesion. Biopsy of the lesion revea...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Morton SJ,Midthun K,Merz WG

    更新日期:1986-12-01 00:00:00

  • Structure and function of major histocompatibility complex.

    abstract::The major histocompatibility complex (MHC) contains genes that control the structure of many important cell surface antigens and influence a variety of important biological functions. The structures of the MHC in the human, rat and mouse show a remarkable similarity both in terms of the location of their genes and the...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Gill TJ 3rd

    更新日期:1980-11-01 00:00:00

  • Mixed ductal-endocrine carcinoma of the pancreas: a possible pathogenic mechanism for arrhythmogenic right ventricular cardiomyopathy.

    abstract::We describe herein a case of a mixed ductal-endocrine pancreatic carcinoma. Rare cases of mixed pancreatic tumors have been described, with endocrine and exocrine components each making up a significant proportion of the neoplasm; to our knowledge, only one case has been reported with a mixed liver metastasis. In our ...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:10.1043/0003-9985(2000)124<0284:MDECOT>2.0.CO;2

    authors: Leteurtre E,Brami F,Kerr-Conte J,Quandalle P,Lecomte-Houcke M

    更新日期:2000-02-01 00:00:00

  • Giant cell pneumonia caused by varicella zoster virus in a neonate.

    abstract::A premature male neonate, born at the 25th gestational week, developed pneumonia six days after delivery and died. Postmortem examination of the lungs revealed giant cell pneumonia with intranuclear inclusion bodies; varicella zoster infection was confirmed by immunoperoxidase stain using monoclonal antibody to varice...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Saito F,Yutani C,Imakita M,Ishibashi-Ueda H,Kanzaki T,Chiba Y

    更新日期:1989-02-01 00:00:00

  • HER-2/neu oncogene expression and DNA ploidy analysis in breast cancer.

    abstract::This study was performed to evaluate the correlation between HER-2/neu gene expression and DNA ploidy patterns. Forty-five cases of breast-cancer were analyzed. Immunohistochemical staining of HER-2/neu protein on frozen sections was used to detect the HER-2/neu protein, and the Feulgen DNA staining method was used to...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Bacus SS,Bacus JW,Slamon DJ,Press MF

    更新日期:1990-02-01 00:00:00

  • Benign chondrolipomatous tumor of the human female breast.

    abstract::A benign chondrolipomatous breast tumor occurred in a 66-year-old woman. The preoperative diagnosis, based on mammography and xeroradiography, was fibroadenoma. Grossly, the demarcated lesion resembled a fibroadenoma with islands of cartilage projecting from its cut surface. Histologically, it was composed of benign m...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Kaplan L,Walts AE

    更新日期:1977-03-01 00:00:00

  • Myelodysplastic syndromes in children: a critical review of issues in the diagnosis and classification of 887 cases from 13 published series.

    abstract:CONTEXT:Pediatric myelodysplastic syndromes (MDSs) are uncommon disorders, which may be difficult to diagnose, particularly in the absence of increased blasts. Pediatric MDSs have several unique features including their association with inherited/constitutional disorders in approximately one third of patients. The clas...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章,评审

    doi:10.1043/1543-2165(2007)131[1110:MSICAC]2.0.CO;2

    authors: Elghetany MT

    更新日期:2007-07-01 00:00:00

  • The use of a commercially available enzyme immunoassay for the detection of Clostridium difficile toxin A.

    abstract::A commercially available enzyme immunoassay (EIA) for the detection of Clostridium difficile toxin A (Premier Toxin A EIA, Meridian Diagnostics, Cincinnati, Ohio) was compared with tissue culture cytotoxicity assay, enterotoxigenic culture, and latex agglutination test for the laboratory diagnosis of C difficile-assoc...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Gilligan PH,Walden TP,Kelly WF,Wait KJ,Kraft JA,Willis DH

    更新日期:1993-05-01 00:00:00

  • Erythroblast multinuclearity in bone marrow and spleen. Congenital dyserythropoietic anemia-like abnormalities without functional evidence of dyserythropoiesis.

    abstract::A dyserythropoietic syndrome with coincidental immune thrombocytopenia seen during pregnancy is discussed. The morphological and serological results in this case most resemble type II congenital dyserythropoietic anemia. However, functional evidence of dyserythropoiesis was absent and the patient was not anemic. Splen...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Lillicrap DP,Corbett WE,Giles AR,Ginsburg AD

    更新日期:1987-06-01 00:00:00

  • Interpretive criteria of the Western blot assay for serodiagnosis of human immunodeficiency virus type 1 infection.

    abstract::This project was designed to evaluate different criteria used in the interpretation of the human immunodeficiency virus type 1 (HIV-1) Western blot assay on a group of serum samples blinded to the examiner that were collected from individuals attending three different public health departments in central North Carolin...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: O'Gorman MR,Weber D,Landis SE,Schoenbach VJ,Mittal M,Folds JD

    更新日期:1991-01-01 00:00:00

  • Proficiency testing of enzymes. Charting the way toward standardization.

    abstract::Laboratories participating in the College of American Pathologists Enzyme Survey (ES) and Comprehensive Chemistry Survey used diverse methods for the same analyte, resulting in a considerable range of values for the commonly performed enzyme measurements. Nevertheless, with the techniques developed for the ES, both th...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Lott JA,Tholen DW,Massion CG

    更新日期:1988-04-01 00:00:00

  • Immunofluorescence for serodiagnosis of retrovirus infection.

    abstract::Indirect immunofluorescence antibody testing is a mainstay of retrovirus serodiagnosis in the public health community, affording quick, inexpensive, and clear results with significant advantages over Western blot testing. Limitations regarding training of personnel and availability of reagents will probably continue a...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 历史文章,杂志文章,评审

    doi:

    authors: Ascher MS,Wilber JC

    更新日期:1990-03-01 00:00:00

  • Ethical issues and the breast cancer patient.

    abstract::The association of cancer and death in laypeoples' thinking has resulted in discussions of cancer diagnoses often being held sub rosa. Open acceptance of a diagnosis of cancer cannot only help to dispel associated fears but also can serve to educate other persons to recognize that cancers can be cured. Open discussion...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Cummings NB

    更新日期:1994-11-01 00:00:00

  • Errors in transfusion medicine. Detection, analysis, frequency, and prevention.

    abstract::The Mayo Clinic (Rochester, Minn) Division of Transfusion Medicine evaluated the effect of methods of error detection, analysis, and prevention on the rate of errors occurring from 1982 through 1992. We defined an error as any deviation from the standard operating procedure. Twenty-four standard operating procedures w...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Taswell HF,Galbreath JL,Harmsen WS

    更新日期:1994-04-01 00:00:00

  • Human Papillomavirus-Related Carcinoma With Adenoid Cystic-like Features of the Sinonasal Tract (Also Known as Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma).

    abstract::Human papillomavirus (HPV)-related carcinoma with adenoid cystic-like features is a rare, recently recognized entity restricted to the sinonasal tract. By definition, it is associated with high-risk HPV infection, particularly with HPV type 33. In most cases, tumors are composed of dual cell populations, including pre...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章,评审

    doi:10.5858/arpa.2018-0027-RS

    authors: Chen CC,Yang SF

    更新日期:2019-11-01 00:00:00

  • Large cell neuroendocrine carcinoma of the ampulla of vater.

    abstract::We report a large cell neuroendocrine carcinoma arising in the ampulla of Vater. The patient, a 74-year-old woman, presented with a 3-cm ulcerated mass located in the ampullary region. She died of disease 8 months after surgery. Microscopically, the tumor was extensively necrotic. It was composed of islands and trabec...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:10.1043/0003-9985(2003)127<221:LCNCOT>2.0.CO;2

    authors: Cavazza A,Gallo M,Valcavi R,De Marco L,Gardini G

    更新日期:2003-02-01 00:00:00

  • The endometrium.

    abstract:CONTEXT:Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these specimens. OBJECTIVE:To emphasize practical aspects of endometrial specimen handling and reporting, with selected comments on common diagnostic pit...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章,评审

    doi:10.1043/1543-2165(2007)131[372:TE]2.0.CO;2

    authors: Silverberg SG

    更新日期:2007-03-01 00:00:00

  • Primary tracheal neurilemoma: report of a case with ultrastructural examination.

    abstract::A case of tracheal neurilemoma that was removed by segmental tracheal resection was studied. Only seven other cases of benign neurogenic tracheal tumor (three neurofibromas and four neurilemomas) were found in the literature. Failure to consider this rare tracheal tumor as a cause of respiratory distress has frequentl...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Ma CK,Raju U,Fine G,Lewis JW Jr

    更新日期:1981-04-01 00:00:00

  • Immunohistochemical analysis of proteins of the Bcl-2 family in pulmonary lymphangioleiomyomatosis: association of Bcl-2 expression with hormone receptor status.

    abstract:BACKGROUND:Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women, is characterized by proliferation of abnormal smooth muscle cells (LAM cells), which often differ from normal pulmonary smooth muscle cells by frequently having estrogen and progesterone receptors. OBJECTIVE:To evaluate the relationships am...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 临床试验,杂志文章

    doi:

    authors: Usuki J,Horiba K,Chu SC,Moss J,Ferrans VJ

    更新日期:1998-10-01 00:00:00

  • Expression of Galectin-3 in renal neoplasms: a diagnostic, possible prognostic marker.

    abstract:CONTEXT:Galectin-3, a member of the lectin family, was shown to be expressed in normal distal tubular cells and in renal cell carcinomas (RCC). However, its diagnostic and prognostic significance in RCC is as yet undefined. OBJECTIVES:To describe the expression of Galectin-3 among different histologic subtypes of rena...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:10.1043/2008-0392-OAR1.1

    authors: Dancer JY,Truong LD,Zhai Q,Shen SS

    更新日期:2010-01-01 00:00:00

  • Drug-specific Fab therapy in drug overdose.

    abstract::The use of digoxin-specific fragments, antigen-binding (Fab) for antidotal therapy of severe digitalis intoxication is rapidly becoming a treatment of choice. Furthermore, studies with this mode of drug-specific therapy using Fab specific for desipramine and for phencyclidine suggest that this treatment may be applica...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Hursting MJ,Raisys VA,Opheim KE

    更新日期:1987-08-01 00:00:00

  • Methyldopa-induced liver injury. Rapid progression to fatal postnecrotic cirrhosis.

    abstract::A 55-year-old woman developed symptoms suggestive of hepatitis 12 weeks after first receiving methyldopa for hypertension. Liver biopsy showed chronic aggressive hepatitis with subacute hepatic necrosis. Methyldopa was discontinued, but after exhibiting transient clinical improvement, the patient's condition progressi...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Thomas E,Bhuta S,Rosenthal WS

    更新日期:1976-03-01 00:00:00

  • Apoptosis and necrosis. Basic types and mechanisms of cell death.

    abstract::Apoptosis and necrosis are two fundamental types of cell death. Current knowledge indicates that the key mechanism of apoptosis is endonuclease activation leading to internucleosomal double-stranded chromatin (DNA) breaks, whereas the key mechanism of necrosis is cell membrane damage. The initial alterations of cellul...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章,评审

    doi:

    authors: Buja LM,Eigenbrodt ML,Eigenbrodt EH

    更新日期:1993-12-01 00:00:00

  • Fatal intestinal pseudo-obstruction in brown bowel syndrome.

    abstract::A 52-year-old man, suffering for years from malabsorption due to endemic sprue, developed progressive bowel dysfunction, ie, recurrent ileus and intestinal pseudo-obstruction. Because of partial volvulus formation, ileocecal resection was performed. Histopathologic examination of the resected specimen revealed signs o...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Ruchti C,Eisele S,Kaufmann M

    更新日期:1990-01-01 00:00:00

  • Gastric toxoplasmosis in a patient with acquired immunodeficiency syndrome. A case report and review of the literature.

    abstract::Toxoplasmosis is a common opportunistic pathogen in patients with acquired immunodeficiency syndrome (AIDS). It usually presents with ocular, central nervous system, or pulmonary disease. Gastric toxoplasmosis is uncommon in AIDS patients, especially in the absence of central nervous system manifestations. In the few ...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章,评审

    doi:10.1043/1543-2165(2003)127<732:GTIAPW>2.0.CO;2

    authors: Ganji M,Tan A,Maitar MI,Weldon-Linne CM,Weisenberg E,Rhone DP

    更新日期:2003-06-01 00:00:00

  • Communicating critical values in anatomic pathology.

    abstract::Critical values in anatomic pathology are usually information sensitive, whereas most such values in laboratory medicine are time sensitive. However, there is an important time element in anatomic pathology as well. Pathologists should be aware that many medicolegal actions against radiologists are based on failure to...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:10.1043/1543-2165(2006)130[641:CCVIAP]2.0.CO;2

    authors: LiVolsi VA,Leung S

    更新日期:2006-05-01 00:00:00

  • p53 gene mutations and p53 protein expression in human soft tissue sarcomas.

    abstract:OBJECTIVE:To determine the frequency of mutation and overexpression of the p53 tumor suppressor gene in human soft tissue sarcomas. DESIGN:A total of 31 soft tissue sarcomas were analyzed by immunohistochemistry for the expression of p53 protein and were subsequently investigated by the polymerase chain reaction techn...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Yoo J,Lee HK,Kang CS,Park WS,Lee JY,Shim SI

    更新日期:1997-04-01 00:00:00

  • Adenomatoid tumor of the uterus. Ultrastructural, histochemical, and immunohistochemical analysis.

    abstract::A uterine tumor from a 34-year-old woman was investigated morphologically and immunohistochemically. The tumor tissue was composed of multiple cystic spaces of various sizes. The cyst wall was covered by a single layer or occasionally multiple layers of flattened cells. Electron micrographs of the tumor tissue reveale...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:

    authors: Suzuki T,Yoshida Y,Kaku T,Kikuchi K,Mori M

    更新日期:1985-11-01 00:00:00

  • Primary small bowel carcinoid tumor with bilateral breast metastases: report of 2 cases with different clinical presentations.

    abstract:CONTEXT:Carcinoid tumor metastatic to the breast is uncommon and can closely mimic a mammary carcinoma. The differentiation of metastatic carcinoid tumor from primary breast tumor is important, however, owing to different clinical management and prognosis. OBJECTIVE:The purpose of this study was to describe 2 patients...

    journal_title:Archives of pathology & laboratory medicine

    pub_type: 杂志文章

    doi:10.1043/1543-2165(2004)128<292:PSBCTW>2.0.CO;2

    authors: Mosunjac MB,Kochhar R,Mosunjac MI,Lau SK

    更新日期:2004-03-01 00:00:00