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A K Lee

Publications and source records attributed to A K Lee.

At least 37 records · Page 2Linked to original sources
PubMed1998

Arginine vasopressin triggers intracellular calcium release, a calcium-activated potassium current and exocytosis in identified rat corticotropes.

Arginine vasopressin (AVP) stimulates the secretion of ACTH from pituitary corticotropes. We investigated the action of AVP in single corticotropes of male rats. Corticotropes were identified with the reverse hemolytic plaque assay using antibodies against ACTH. Using the whole-cell recording technique in conjunction with the fluorescent Ca2+ indicator, indo-1 to measure the concentration of cytosolic free Ca2+ ([Ca2+]i), we show that AVP triggers a transient and plateau pattern of Ca2+ signal. The [Ca2+]i elevation activates the apamin-sensitive Ca2+-activated K+ current, which, in turn, causes membrane hyperpolarization. The Ca2+ signal can be elicited in the absence of extracellular Ca2+ and is mimicked by intracellular inositol 1,4,5-trisphosphate (IP3). Both GDP-beta-S and heparin inhibit the AVP response. Thus, AVP triggers intracellular Ca2+ release from the (IP3)-sensitive store via a GTP binding protein-coupled phosphoinositide pathway. Using the high temporal resolution capacitance measurement to detect exocytosis in single corticotropes, we show that a burst of exocytosis is evoked during the AVP-triggered [Ca2+]i elevation. Exocytosis can also be triggered when Ca2+ is released directly from the IP3-sensitive store via flash photolysis of caged IP3. We conclude that AVP-stimulated ACTH secretion in rat corticotrophs is closely coupled to intracellular Ca2+ release from the IP3-sensitive store.

Animals↗
PubMed1997

Mechanism underlying corticotropin-releasing hormone (CRH) triggered cytosolic Ca2+ rise in identified rat corticotrophs.

1. The patch-clamp technique was used in conjunction with the fluorescent Ca2+ indicator indo-1 to measure simultaneously cytosolic Ca2+ concentration ([Ca2+]i) and membrane potential in single rat corticotrophs identified with the reverse haemolytic plaque assay. 2. Application of the adrenocorticotropin (ACTH) secretagogue, corticotropin-releasing hormone (CRH), triggered a sustained [Ca2+]i elevation and membrane depolarization. 3. The CRH action was mediated via the cAMP-dependent protein kinase cascade. Both the CRH-induced depolarization and [Ca2+]i elevation could be mimicked by extracellular application of the adenylate cyclase activator forskolin or the membrane-permeable cAMP analogue, 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphate (8-CPT-cAMP). Intracellular adenosine cyclic 3',5'-(Rp)-phosphothioate (Rp-cAMPS), a protein kinase A inhibitor, abolished the CRH effects. 4. Voltage-clamp studies suggest that the CRH-triggered depolarization was due to the reduction of background K+ conductances. The CRH-sensitive current was Ca2+ independent and was insensitive to the K+ channel blockers tetraethylammonium (TEA) or 4-aminopyridine (4-AP), but could be partially inhibited by Ba2+. 5. The CRH-triggered steady-state depolarization stimulated extracellular Ca2+ entry via voltage-gated Ca2+ channels and raised [Ca2+]i. CRH failed to stimulate [Ca2+]i rise in cells that were voltage clamped at their resting potential. Removal of extracellular Ca2+ or inhibition of Ca2+ channels by Ni2+ abolished the [Ca2+]i rise. 6. Voltage-clamp studies of voltage-gated Ca2+ channels using Ba2+ as charge carrier show that approximately 90% of the channels were available for activation at the resting potential. CRH did not enhance the voltage-gated Ca2+ channels.

Animals↗
PubMed1997

Lymph node negative invasive breast carcinoma 1 centimeter or less in size (T1a,bNOMO): clinicopathologic features and outcome.

BACKGROUND: Patients with lymph node negative invasive breast carcinomas < or = 1 cm in size have a low recurrence rate and may be spared adjuvant therapy. Reliable prognostic features will help physicians design appropriate treatment for these patients. METHODS: The clinicopathologic features, prognostic marker profiles, and clinical outcomes of 88 T1a,bN0M0 carcinomas in 87 patients who presented between 1975 and 1990 were studied. The size of each tumor was determined by direct measurement of histologic sections. The median follow-up was 7.8 years (range, 4-15 years). The characteristics of tumors diagnosed between 1975 and 1983 and between 1984 and 1990 were also compared. RESULTS: Before 1984, the majority of patients presented with palpable mass lesions, whereas from 1984 on, more patients presented with mammographic abnormalities. However, no significant differences in the pathologic features of tumors were observed between the two periods. There were only 3 locoregional recurrences (3%) and 4 distant recurrences (5%). Palpable tumors had worse prognoses than mammographically detected lesions (P = 0.02). Histologic grade, lymphatic invasion, hormone receptors, Ki-67 antigen, and bcl-2 expression were significant univariate prognostic indicators. The small number of patients in the series precluded multivariate analysis. None of the 43 patients (49%) with tumors < or = 0.5 cm, or of histologic and nuclear Grade 1, or of favorable histologic types developed recurrences; and their outcomes were significantly better than those of other patients (P = 0.013). Tumors originally classified as T1b, but which exceeded 1 cm on review and were excluded from the study, had a significantly higher distant recurrence rate (23%) than bona fide T1a,b carcinomas (P = 0.03). CONCLUSIONS: T1a,bN0M0 carcinomas have a low recurrence rate, especially those tumors < or = 0.5 cm, or of low histologic or nuclear grade, or of favorable histologic type. The high recurrence among patients with tumors initially understaged as T1a,b carcinoma underscores the importance of accurately determining tumor size.

Adult↗
PubMed1996

Dopamine (D2) receptor regulation of intracellular calcium and membrane capacitance changes in rat melanotrophs.

1. Indo-1 microfluorimetry and patch clamp techniques were used to study the decrease in cytosolic [Ca2+] ([Ca2+]i) caused by dopamine (D2) receptor activation and the calcium dependence of membrane capacitance changes in single rat melanotrophs. 2. [Ca2+]i decreased when extracellular calcium was removed or when the calcium channel blockers nickel (2 mM) or cadmium (100 microM) were applied by bath perfusion. 3. Quinpirole, a dopamine (D2) receptor agonist, reduced [Ca2+]i by 55 +/- 9 nM and hyperpolarized membrane potential by 29 +/- 9 mV simultaneously. 4. Quinpirole-induced [Ca2+]i decrease required deactivation of voltage-dependent calcium channels. Voltage clamping the membrane potential at -25 mV prevented the quinpirole-induced [Ca2+]i decrease. Nickel (2 mM) reduced [Ca2+]i without hyperpolarization and precluded additional [Ca2+]i decrease by quinpirole. 5. Membrane capacitance measurement of secretion rates in cells dialysed with buffered calcium solutions showed that secretion began at approximately 400 nM Cai2+. 6. Melanotrophs have IP3-sensitive calcium stores, but no caffeine-sensitive calcium stores. Calcium released from IP3-sensitive calcium stores also stimulated secretion. 7. Secretion in melanotrophs is modulated by protein kinase activators. cAMP (200 microM) enhanced secretion at [Ca2+]i > 1000 nM. Phorbol myristate acetate (PMA; 200 nM) enhanced secretion at [Ca2+]i < 400 nM, but not in the absence of calcium. 8. Dopamine receptor activation can reduce secretion by reducing the calcium influx through calcium channels with hyperpolarization of the membrane potential. However downregulation of either cAMP or protein kinase C activity may also contribute to the decrease in secretion.

Animals↗
PubMed1996

Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome.

BACKGROUND: Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome. METHODS: Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival. RESULTS: Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival. CONCLUSIONS: Male breast carcinoma presents in an advanced stage with less favorable survival, despite low histologic grade, high estrogen receptor content, and small size. Anatomic factors may have been responsible for the poor survival outcome (i.e., paucity of breast tissue and close tumor proximity to skin and nipple, facilitating dermal lymphatic spread and early regional and distant metastasis).

Adenocarcinoma↗
PubMed1996

Controversies in the treatment of ductal carcinoma in situ.

In summary, certain subgroups of DCIS appear not to require radiation. Corroboration of these results from retrospective reviews and prospective trials is necessary to confirm the safety and efficacy of individualized treatment strategies. Even though the current standard of treatment is (1) lumpectomy with radiation therapy, (2) mastectomy, or (3) mastectomy with reconstruction, it is possible in the future to say that patients with low-grade DCIS (the exact criteria to be defined) may be eligible for breast conservation without radiation, and all patients with high-grade DCIS or perhaps low-grade DCIS with necrosis would be treated best by lumpectomy plus radiation. It is possible that a small subgroup of patients may be best treated by mastectomy, or perhaps, as the results of B-24 become available, by radiation therapy plus tamoxifen. The use of tumor markers such as c-erbB-2, cathepsin D, and NM 23 may help us to better define these subgroups, but much study is necessary before a definite treatment strategy is reached.

Biomarkers, Tumor↗
PubMed1996

The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast.

The differential expression of keratins in myoepithelial and epithelial cells of the breast makes immunohistochemical distinction of lesions an attractive possibility. High molecular weight keratin, 34BE12, is a monoclonal antibody that recognizes keratins 1, 5, 10, and 14. Because myoepithelial cells predominantly express keratins 5 and 14 and epithelial cells predominantly express keratins 8 and 18, it is natural to assume that 34BE12 may be a good marker of myoepithelial cells but not epithelial cells. However, recent studies of the breast have reported conflicting results. To determine the potential role of 34BE12 in the breast, we studied by immunohistochemistry 19 tubular carcinomas, 14 radial scars, two microglandular adenoses, and 9 sclerosing adenoses, using monoclonal antibodies to high molecular weight keratin, smooth muscle actin, type IV collagen, and antiserum to S100 protein. Actin was negative in all 19 (100%) tubular carcinomas, but it delineated the myoepithelial cells in 22 of 23 (95.6%) benign lesions of sclerosing adenosis and radial scars; it was also negative in microglandular adenosis. In comparison, epithelial cytoplasmic 34BE12 reactivity was seen in 3 of 19 (15.8%) tubular carcinomas, whereas myoepithelial cells failed to react in 4 of 23 (17.3%) benign conditions. Antiserum to S100 protein had a similar disadvantage of labeling both epithelial and myoepithelial cells with reactivity in 5 of 19 (26.3%) tubular carcinomas. In microglandular adenosis, the epithelial cells were strongly S100 protein positive and focally 34BE12 positive, but no staining was observed for actin. Type IV collagen staining outlined distinct basement membranes in microglandular adenosis and other benign conditions but not in tubular carcinomas. However, staining for type IV collagen requires enzymatic pretreatment and is difficult to perform, especially in sclerotic breast tissue. In conclusion, actin appears to be the most consistent and specific marker for distinguishing tubular carcinomas from other benign conditions, and type IV collagen has a contributory role, whereas 34BE12 is less valuable than in prostatic biopsies.

Actins↗
PubMed1995

Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations.

Angiogenesis is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of prognostic value in several types of malignancies. Scarce data are available on angiogenesis in gastrointestinal tumors. We studied 36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation. Endothelial cells were immunostained with an anti-CD31 mAb; in each case three microscopic fields (x 200) with the highest number of microvessels were counted: the average value of the three fields was used to evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41 cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001; adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with metastases, disease stage, and patient survival. The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis. MVD, however, does not provide significant prognostic information in colorectal cancer patients.

Adenocarcinoma↗
PubMed1995

CDC25 phosphatases as potential human oncogenes.

Cyclin-dependent kinases (CDKs) are activated by CDC25 phosphatases, which remove inhibitory phosphate from tyrosine and threonine residues. In human cells, CDC25 proteins are encoded by a multigene family, consisting of CDC25A, CDC25B, and CDC25C. In rodent cells, human CDC25A or CDC25B but not CDC25C phosphatases cooperate with either Ha-RASG12V or loss of RB1 in oncogenic focus formation. Such transformants were highly aneuploid, grew in soft agar, and formed high-grade tumors in nude mice. Overexpression of CDC25B was detected in 32 percent of human primary breast cancers tested. The CDC25 phosphatases may contribute to the development of human cancer.

Animals↗
PubMed1995

The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas.

Colorectal adenocarcinomas may display features of endocrine differentiation, shown by argyrophil stains and by the expression of endocrine markers such as chromogranin A. We investigated chromogranin A and secretogranin II immunoreactivity in a series of 208 carcinomas of the large bowel to assess the prevalence and clinical significance of endocrine differentiation. Tumors expressing endocrine markers were classified as low expressors (< than 1 immunoreactive tumour cell/mm2) and high expressors (> than 1 immunoreactive tumour cell/mm2). There were 33 (16%) carcinomas showing both chromogranin A and secretogranin II immunoreactivity: 11 tumours (5%) were high expressors. Endocrine differentiation was not related to the disease stage, tumour location, grade, DNA ploidy and p53 protein accumulation. In the entire series chromogranin A immunoreactivity did not provide prognostic information using univariate and multivariate analysis. A worse overall survival (P = 0.048) was demonstrated for the stage III patients with high expressor tumours, but there were only five patients in this group. The results of our investigation suggest that chromogranin A immunoreactivity is not a useful variable in the prognostic assessment of colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1995

bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas.

The bcl-2 gene is an oncogene that inhibits programmed cell death (apoptosis). We investigated by immunocytochemistry bcl-2 expression in normal colonic mucosa, hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. The purpose of the investigation was twofold; to assess the possible role of bcl-2 in colorectal tumorigenesis and to evaluate its clinical significance. The cases studied included 24 hyperplastic polyps, 49 adenomas, and 205 colorectal carcinomas. In both normal mucosa and hyperplastic polyps bcl-2 immunoreactivity was detected only in the proliferative cells of the colonic crypts. Conversely, bcl-2 immunoreactivity was noted in all adenomas irrespective of the degree of dysplastic change; it was diffuse in 84% of adenomas and focal in the remaining cases. In colorectal carcinomas bcl-2 expression was undetectable in 50% and focal (less than 50% immunostained neoplastic cells) in 38% of tumors. The remaining 12% of the carcinomas displayed diffuse (more than 50% immunostained neoplastic cells) bcl-2 immunoreactivity. In colorectal carcinomas bcl-2 expression was not correlated with relevant clinicopathologic parameters, including disease stage, tumor location and growth fraction, DNA ploidy, and p53 protein accumulation, and had no prognostic significance by univariate or multivariate analysis. These results suggest that bcl-2 oncoprotein may play a role in colorectal tumorigenesis, probably in the early phases of the adenoma-carcinoma sequence. bcl-2 expression in established tumors has no prognostic significance.

Adenocarcinoma↗
PubMed1995

Hot flushes in men with pituitary adenoma.

BACKGROUND: Hot flushes are common in menopausal women and also in men made acutely hypogonadal after orchiectomy or testicular injury. It is, however, an unusual symptom in patients with hypogonadism secondary to pituitary tumors. METHODS: In evaluating the histories of men with hypogonadal state associated with nonfunctioning pituitary macroadenoma we were struck by the presence of hot flushes in four of them. RESULTS: All four of the patients were hypogonadal with sexual dysfunction preoperatively. All had low gonadotropins and low testosterone levels with varying degrees of panhypopituitarism. All had successful transsphenoidal removal of tumors. None had endocrine improvement following surgery. All patients had improvement in sexual function and the hot flushes with administration of testosterone postoperatively. CONCLUSIONS: Hot flushes are an uncommon presentation in men with pituitary adenoma. Perhaps the symptom will become more prominent if it is specifically questioned. We postulate that the cause of the flushing is related to nonsuppressed pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus.

Adenoma↗
PubMed1995

p53 gene mutations, p53 protein accumulation and compartmentalization in colorectal adenocarcinoma.

p53 accumulation may occur in the nucleus and/or cytoplasm of neoplastic cells. Cytoplasmic accumulation has been reported to be an unfavorable, but not established, prognostic indicator in colorectal cancer. Different types of p53 intracellular compartmentalization could depend either on p53 gene mutations or on the interaction with p53 protein ligands. The purposes of our study were (1) to assess whether the different patterns of p53 accumulation are selectively associated with p53 mutations and (2) to evaluate the clinical significance of p53 mutations in colorectal carcinomas. We evaluated p53 gene mutations in colorectal carcinomas. We evaluated p53 gene mutations in exons 5 through 8, by polymerase chain reaction and single-strand conformation polymorphism analysis; p53 accumulation and intracellular compartmentalization were detected immunocytochemically with the antibodies PAb1801 and CM1. p53 mutations were found in 74 of 126 carcinomas (59%). Nuclear p53PAb1801 accumulation was associated with p53 gene mutations (P < 0.001) whereas cytoplasmic p53 CM1 accumulation was more likely to occur with the wild-type p53 gene (P = 0.048). Overall, 112 carcinomas (89%) displayed p53 gene mutations and/or p53 accumulations of any type. p53 mutations were not correlated with important clinicopathological parameters and were not related to patient survival. Our data suggest that mechanisms other than mutations may also play a role in inhibiting p53 tumor-suppressing functions in colorectal carcinomas. Cytoplasmic p53CM1 accumulation frequently does not depend on p53 mutations.

Adenocarcinoma↗
PubMed1994

Ductal carcinoma in situ of the male breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the male breast is an uncommon disease, accounting for approximately 7% of all male breast carcinomas. Compared with invasive carcinomas of the breast, the prognosis associated with DCIS in men is excellent; however, clinical features, pathology, and treatment of this disease are not well defined in the literature. METHODS: Records of 23 men with carcinoma of the breast treated at the Lahey Clinic from 1968 to 1991 were reviewed, revealing 4 patients with pure DCIS (17%). The reported management of DCIS in women is discussed in comparison with that of DCIS in men. RESULTS: Of the four patients with DCIS, the presenting complaint was a retroareolar mass in three patients and a bloody nipple discharge in one patient. The pathologic subtype was papillary in one patient and intracystic papillary in three patients. Two patients were treated with partial mastectomy alone. Disease recurred locally as DCIS in both patients, requiring mastectomy at 30 and 108 months. No lymph node metastases were found in the three patients who underwent axillary dissection. All four patients were alive without disease at 133, 120, 36, and 32 months of follow-up, respectively. CONCLUSIONS: Although the sample size was small, our patients and a review of the literature suggest that most DCIS in men is of the papillary type and that mastectomy without axillary dissection is the preferred treatment.

Adenocarcinoma↗
PubMed1994

Cyclic GMP-dependent protein kinase activity in rat pulmonary microvascular endothelial cells.

Cyclic GMP-dependent protein kinase (cGPK) activity was determined in rat pulmonary microvascular endothelial cells (RPMVEC) using cGMP-stimulated phosphorylation of BPDEtide and histone F2B substrates in the presence of PKI [peptide inhibitor of cAMP-dependent protein kinase (cAPK)]. RPMVEC cGPK activity was localized to the 100,000 x g cytosolic fraction. The EC50 for cGMP activation in the presence of PKI was 0.16 microM and H-89 inhibition under similar conditions showed an IC50 value of 0.16 microM. Anion-exchange chromatography of RPMVEC and rat lung cytosolic fractions showed separation of the cGMP-dependent from the cGMP-independent protein kinase activity and similar elution conductivities. Further, Western blots of RPMVEC active DEAE-Trisacryl fractions showed immunoreactivity using bovine Type I cGPK antiserum. Preliminary studies reveal six potential substrates phosphorylated by cGPK in RPMVEC. These studies describe an endothelial cell (EC) cGMP-receptor, cGPK, in addition to cGMP-activated (Type II) phosphodiesterase (PDE).

Amino Acid Sequence↗
PubMed1994

Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas.

BACKGROUND: Aberrations of the p53 gene (also known as TP53) frequently lead to the synthesis of mutant proteins that accumulate in the nuclei and/or cytoplasm of neoplastic cells. Intracellular p53 protein accumulation may be an unfavorable prognostic parameter in breast, lung, ovarian, gastric, and colorectal cancers. Specific classes of p53 gene mutations, assayed by characteristic subcellular p53 protein accumulation patterns, may be useful prognostic indicators. PURPOSE: The prognostic value of nuclear and cytoplasmic p53 protein accumulation in the tumor cells of patients with colorectal carcinoma was studied. METHODS: Antibodies PAb 1801 and CM1 were used for immunocytochemical assay of nuclear and cytoplasmic p53 protein accumulation in a retrospective series of colorectal carcinoma samples obtained from 206 patients who were followed for at least 5 years. Results were correlated with the following clinicopathologic parameters: patient sex and age; tumor site, stage, and grade; and DNA ploidy status of the tumors. Overall survival and disease-free survival were analyzed with the Kaplan-Meier method. Differences in distributions were analyzed using the Mantel-Cox method. Multivariate analysis was performed with the Cox proportional hazards model. RESULTS: Immunostaining with PAb 1801 revealed nuclear p53 accumulation in 46% (95) of 206 cases, whereas CM1 immunostaining of 197 cases showed nuclear and cytoplasmic p53 accumulation in 33% (65 cases) and 50% (99 cases) of the cases, respectively. In univariate analysis, both nuclear p53PAb 1801 and cytoplasmic p53CM1 protein accumulations were significantly associated with poor overall survival (P = .0198 and P = .0017, respectively) and with disease-free survival (P = .004 and P = .0016, respectively). When patients were analyzed according to site of their tumors, nuclear p53PAb 1801 protein accumulation was statistically significant only in the right colon (P = .027), whereas cytoplasmic p53CM1 protein accumulation was statistically significant in the left colon and rectum (P = .0016). In multivariate analysis, only cytoplasmic p53CM1 protein accumulation was associated with poor overall survival and with disease-free survival (P = .006 and P = .002, respectively). With the addition of DNA ploidy status, however, cytoplasmic p53CM1 protein accumulation remained significant only for disease-free survival (P = .035). In patients with tumors of the left colon and rectum, cytoplasmic p53CM1 protein accumulation was the most significant prognostic indicator for overall survival (P = .007) and disease-free survival (P = .002) after disease stage. CONCLUSION: Cytoplasmic p53CM1 protein accumulation, but not nuclear p53PAb 1801 protein accumulation, is an independent prognostic parameter in patients with colorectal carcinomas. IMPLICATIONS: Cytoplasmic p53CM1 accumulation may be a useful indicator of patients at high risk for disease recurrence who may benefit from aggressive adjuvant therapy.

Adenocarcinoma↗